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Sample records for lilli paarma hannu

  1. Drotrecogin alfa Eli Lilly.

    Science.gov (United States)

    de Jonge, E

    2002-04-01

    Drotrecogin alfa (Xigris, recombinant activated protein C) is an anticoagulant developed and launched by Eli Lilly & Co for the treatment of sepsis [333781], [339372], [430133], [436271]. The FDA and the EMEA accepted the brand name Xigris for drotrecogin alfa in June 2001. This trade name had been proposed by Lilly in place of the previous brand name, Zovant, which was deemed unacceptable by the EMEA due to concerns that the name could be confused with hospital-based drugs [412512]. Filings for sepsis were made in the US, EU and Australia in February 2001 [398514], [447870] and in March 2001, the US FDA assigned drotrecogin alfa Priority Review status [403435]. The FDA extended the action date from July 27 to October 27, 2001 for completion of its review of the biologics license application (BLA) for drotrecogin alfa to assess further supplementary data submitted by Lilly [412512]. At the October 16, 2001 meeting (postponed from September 12), the FDA Advisory Committee on Anti-Infective Drugs split 10 to 10 over whether to recommend approval [425873], [425940]. In late October 2001, Lilly received an approvable letter from the FDA for the treatment of severe sepsis. Approval was contingent upon successful negotiation of labeling, agreement on post-approval clinical trials, and successful completion of manufacturing inspections [427301]. In November 2001, the FDA approved drotrecogin alfa for the reduction of mortality in adult patients with severe sepsis who have a high risk of death [430133]; the product was launched onto the US market days later [436271]. Following the FDA committee's split decision in October 2001, Credit Suisse First Boston, which expected mid-2002 approval but with restrictive labeling, revised its predictions from $1.265 billion in 2004 sharply downwards to $543 million [425929].

  2. Duloxetine Eli Lilly.

    Science.gov (United States)

    Anttila, Sami; Leinonen, Esa

    2002-08-01

    Duloxetine is a serotonin (5-HT) and norepinephrine (NE) uptake inhibitor in pre-registration for depression. In vivo studies demonstrate that duloxetine inhibits 5-HT and NE transporters and this may induce an antidepressant effect [159168]. In humans, duloxetine has a low affinity for most 5-HT subtypes and for muscarinic, histamine H1, alpha1-adrenergic, alpha2-adrenergic and dopamine D2 receptors [444103]. Thus, it is not surprising that the meta-analysis of four recent clinical studies suggests duloxetine is a potent and well-tolerated antidepressant [429723]. By December 2001, Lilly had filed an NDA for depression. The launch of duloxetine is planned for the second half of 2002 [434250], [436220]. In April 2002, filing for stress urinary incontinence was anticipated for later in 2002 [456894]. Analysts at Banc of America predicted in April 2002, that the drug will be launched in the first quarter of 2003. The company projects US $400 million in revenue in 2003 and anticipates duloxetine to reach peak sales of over US $1 billion [450920]. Analysts at Morgan Stanley, projected US $25 million in sales in the fourth quarter 2002, rising to US $900 million in 2006 [450937]. At the same time, Credit Suisse First Boston anticipated launch for late 2002, with US $220 million in duloxetine revenues in 2003 and US $457 million in 2004 [450936].

  3. A Tribute to Graham Lilly

    National Research Council Canada - National Science Library

    John C. Jeffries; Dick Merrill

    2007-01-01

      This year marks the fortieth year of Graham Lilly's service on the faculty of the University of Virginia School of Law and the last - a milestone to be celebrated with admiration and no little sadness...

  4. Analysis list: lilli [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available lilli Cell line + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/lilli.1....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/lilli.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/lilli....10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/lilli.Cell_line.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Cell_line.gml ...

  5. Hannu Mäkelä uus teos otse elust / Jukka Kiho

    Index Scriptorium Estoniae

    Kiho, Jukka

    2008-01-01

    Arvustus: Mäkelä, Hannu. Miisa uus pere / [soome keelest tõlkinud Hille Lagerspetz] ; joonistanud Marika Maijala. Tallinn : Koolibri, 2008. Esitlus 25. aprillil kell 16 Viru Keskuse Rahva Raamatu kaupluses

  6. Luubi all : www.lilly.com / Piret Potisepp

    Index Scriptorium Estoniae

    Potisepp, Piret

    2009-01-01

    Ravimifirma Eli Lilly & Company kogemusi, kuidas uusimate teadusuuringute tulemusi ravimitööstuses kasutades on võimalik arendada jätkusuutlikku tootmist ning laiendada tooteportfelli koostöövõrgustiku kujundamise teel

  7. Luubi all : www.lilly.com / Piret Potisepp

    Index Scriptorium Estoniae

    Potisepp, Piret

    2009-01-01

    Ravimifirma Eli Lilly & Company kogemusi, kuidas uusimate teadusuuringute tulemusi ravimitööstuses kasutades on võimalik arendada jätkusuutlikku tootmist ning laiendada tooteportfelli koostöövõrgustiku kujundamise teel

  8. Modern nonparametric, robust and multivariate methods festschrift in honour of Hannu Oja

    CERN Document Server

    Taskinen, Sara

    2015-01-01

    Written by leading experts in the field, this edited volume brings together the latest findings in the area of nonparametric, robust and multivariate statistical methods. The individual contributions cover a wide variety of topics ranging from univariate nonparametric methods to robust methods for complex data structures. Some examples from statistical signal processing are also given. The volume is dedicated to Hannu Oja on the occasion of his 65th birthday and is intended for researchers as well as PhD students with a good knowledge of statistics.

  9. Eli Lilly and Company's bioethics framework for human biomedical research.

    Science.gov (United States)

    Van Campen, Luann E; Therasse, Donald G; Klopfenstein, Mitchell; Levine, Robert J

    2015-11-01

    Current ethics and good clinical practice guidelines address various aspects of pharmaceutical research and development, but do not comprehensively address the bioethical responsibilities of sponsors. To fill this void, in 2010 Eli Lilly and Company developed and implemented a Bioethics Framework for Human Biomedical Research to guide ethical decisions. (See our companion article that describes how the framework was developed and implemented and provides a critique of its usefulness and limitations.) This paper presents the actual framework that serves as a company resource for employee education and bioethics deliberations. The framework consists of four basic ethical principles and 13 essential elements for ethical human biomedical research and resides within the context of our company's mission, vision and values. For each component of the framework, we provide a high-level overview followed by a detailed description with cross-references to relevant well regarded guidance documents. The principles and guidance described should be familiar to those acquainted with research ethics. Therefore the novelty of the framework lies not in the foundational concepts presented as much as the attempt to specify and compile a sponsor's bioethical responsibilities to multiple stakeholders into one resource. When such a framework is employed, it can serve as a bioethical foundation to inform decisions and actions throughout clinical planning, trial design, study implementation and closeout, as well as to inform company positions on bioethical issues. The framework is, therefore, a useful tool for translating ethical aspirations into action - to help ensure pharmaceutical human biomedical research is conducted in a manner that aligns with consensus ethics principles, as well as a sponsor's core values.

  10. The development of molecularly targeted anticancer therapies: an Eli Lilly and Company perspective.

    Science.gov (United States)

    Perry, William L; Weitzman, Aaron

    2005-03-01

    The ability to identify activated pathways that drive the growth and progression of cancer and to develop specific and potent inhibitors of key proteins in these pathways promises to dramatically change the treatment of cancer: A patient's cancer could be characterized at the molecular level and the information used to select the best treatment options. The development of successful therapies not only requires extensive target validation, but also new approaches to evaluating drug efficacy in animal models and in the clinic compared to the development of traditional cytotoxic agents. This article highlights Eli Lilly and Company's approach to developing targeted therapies, from target identification and validation through evaluation in the clinic. A selection of drugs in the Lilly Oncology pipeline is also discussed.

  11. The Proximal Lilly Collection: Mapping, Exploring and Exploiting Feasible Chemical Space.

    Science.gov (United States)

    Nicolaou, Christos A; Watson, Ian A; Hu, Hong; Wang, Jibo

    2016-07-25

    Venturing into the immensity of the small molecule universe to identify novel chemical structure is a much discussed objective of many methods proposed by the chemoinformatics community. To this end, numerous approaches using techniques from the fields of computational de novo design, virtual screening and reaction informatics, among others, have been proposed. Although in principle this objective is commendable, in practice there are several obstacles to useful exploitation of the chemical space. Prime among them are the sheer number of theoretically feasible compounds and the practical concern regarding the synthesizability of the chemical structures conceived using in silico methods. We present the Proximal Lilly Collection initiative implemented at Eli Lilly and Co. with the aims to (i) define the chemical space of small, drug-like compounds that could be synthesized using in-house resources and (ii) facilitate access to compounds in this large space for the purposes of ongoing drug discovery efforts. The implementation of PLC relies on coupling access to available synthetic knowledge and resources with chemo/reaction informatics techniques and tools developed for this purpose. We describe in detail the computational framework supporting this initiative and elaborate on the characteristics of the PLC virtual collection of compounds. As an example of the opportunities provided to drug discovery researchers by easy access to a large, realistically feasible virtual collection such as the PLC, we describe a recent application of the technology that led to the discovery of selective kinase inhibitors.

  12. John Lilly, The Mind of the Dolphin, and Communication Out of Bounds

    Directory of Open Access Journals (Sweden)

    Bruce Clarke

    2014-09-01

    Full Text Available In this essay I develop a systems-theoretical observation of John Lilly’s cybernetics of communication in his 1967 work The Mind of the Dolphin. The eight-year-old project that The Mind of the Dolphin recounts for public consumption details his aspiration to achieve an unprecedented breakthrough beyond companionate communion to fully abstract linguistic communication across species boundaries. Between 1959 and 1968 Lilly wagered and lost his mainstream scientific career largely over this audacious, ultimately inconclusive bid to establish and document for scientific validation “communication with a nonhuman mind.” In that effort, however, he mobilized the best available tools, a cutting-edge array of cybernetic concepts. He leaned heavily on the information theory bound up with first-order cybernetics and operated with heuristic computational metaphors alongside the actual computers of his era. As I will elicit through some close readings of his texts, in that process Lilly also homed in on crucial epistemological renovations with a constructivist redescription of cognition that may have influenced and motivated his colleague Heinz von Foerster’s more renowned formulations, arriving in the early 1970s, of a second-order cybernetics.

  13. 78 FR 33426 - Eli Lilly and Co.; Withdrawal of Approval of a New Drug Application for ORAFLEX

    Science.gov (United States)

    2013-06-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Eli Lilly and Co.; Withdrawal of Approval of a New Drug... Administration (FDA) is withdrawing approval of a new drug application (NDA) for ORAFLEX (benoxaprofen)...

  14. Kauha : [luuletused] / Pjotr Zahharov ; udmurdi keelest tõlkinud soome keelde Viktor Shibanov, Hannu Oittinen, võru keelde tõlkinud Irina Orehhova, Kauksi Ülle, eesti keelde tõlkinud Taive Särg

    Index Scriptorium Estoniae

    Zahharov, Pjotr

    2005-01-01

    Sisu: Kauha / udmurdi keelest tõlkinud soome keelde Viktor Shibanov, Hannu Oittinen ; Kopsik / udmurdi keelest tõlkinud võru keelde Irina Orehhova, Kauksi Ülle ; Pu-pu : seitse pühendust rähnile 1, 3, 4, 4, 5-7 / udmurdi keelest tõlkinud eesti keelde Irina Orehhova, Taive Särg ; Metamorfoosid 3-8 / udmurdi keelest tõlkinud eesti keelde Irina Orehhova, Taive Särg

  15. Regulating Direct-to-Consumer Drug Information: A Case Study of Eli Lilly's Canadian 40over40 Erectile Dysfunction Campaign.

    Science.gov (United States)

    Pipon, Jean-Christophe Bélisle; Williams-Jones, Bryn

    2015-05-01

    Like most jurisdictions, Canada prohibits direct-to-consumer advertising (DTCA) of prescribed drugs. However, direct-to-consumer information (DTCI) is permitted, allowing companies to inform the public about medical conditions. An analysis of Eli Lilly's 40over40 promotion campaign for erectile dysfunction (ED), which included a quiz on ED, shows that DTCI, like DTCA, can be an effective means of drug familiarization. The pharmaceutical industry is "playing by the rules" currently in effect in Canada. Regulators should thus seriously consider whether existing rules permitting DTCI actually meet stated objectives of protecting the public from marketing campaigns (i.e., DTCA) that may deliver misleading information. Copyright © 2015 Longwoods Publishing.

  16. 氢溴酸2,4-二氯-6-苯基苯氧乙基二乙基胺(Lilly18947)抗克氏锥虫的作用%Trypanocidal action of 2,4- dichloro- 6- phenylphenoxyethyl diethylamine hydrobromide (Lilly 18947) on Trypanosoma cruzi

    Institute of Scientific and Technical Information of China (English)

    Adriana Silvina BERNACCHI; Berta FRANKE de CAZZULO; Jose Alberto CASTRO; Juan Jose CAZZULO

    2002-01-01

    AIM: To study the effect of the inhibitor of cytochrome P450 known as Lilly 18947 (2, 4 dichloro-6 phenylphenoxy ethyl diethylamine ) on Trypanosoma cruzi.METHODS: Trypanosoma cruzi epimastigotes were grown in culture, in absence or in presence of drug.The inhibition of its growth was followed by daily counting using a Neubauer chamber. The effect of Lilly 18947 on the parasite ultrastructure was examined by electron microscopy. To test the effect of different concentrations of drug on the parasite cycle, Vero cells were inoculated with trypomastigotes (RA strain ) and after 72 h the percentage of infected cells and the number of intracellular parasites were estimated and expressed as the endocytic index. RESULTS: Growth of epimastigotes was inhibited by Lilly 18947. Concentrations as low as 50 μmol/L resulted in a complete disappearance of the parasites in culture by the fourth day. With lower concentrations, little growth was observed and total (25μmol/L) or partial lysis (10 μmol/L) were registered by the eighth day of culture. Incubation of epimastigotes with 50 μmol/L of Lilly 18947 resulted in an early damage to cellular structures. Initial signs were dilatation of perinuclear membranes and mitochondria swelling. The infectivity of trypomastigotes to Vero cells in culture was nearly abolished at 15 and 30 μmol/Lconcentrations of the drug. CONCLUSION: Lilly 18947 was able to harm Trypanosoma cruzi membrane functions leading to the loss of its infective properties and its death.

  17. Five eighteenth and nineteenth century books significant in vision science selected from the collection of the Lilly Library at Indiana University.

    Science.gov (United States)

    Goss, David A

    2007-07-01

    This paper discusses five eighteenth and nineteenth century books selected from the collection of the Lilly Library at Indiana University in Bloomington, Indiana. The five were selected because they all contained at least some material of significance in clinical vision science (some contained a broad range of scientific topics) and they were all important publications in their time. The authors of the books, in alphabetical order, were Frans Cornelis Donders, Joseph Priestley, William Charles Wells, Charles Wheatstone, and Thomas Young.

  18. Autobiograafia kui „tõe” diskursus: Lilli Suburgi „Minu saatusega võitluskäik”. Autobiography as the Discourse of “Truth”: Lilli Suburg’s Minu saatusega võitluskäik

    Directory of Open Access Journals (Sweden)

    Eve Annuk

    2012-04-01

    Full Text Available Lilli Suburg (1841-1923 is an author in Estonian literary and cultural history who is not well researched, though her literary output is sufficiently large and her manuscript heritage many-sided, casting light on the little known aspects of her work and activity. Suburg was active in very different fields: she is known as a writer, journalist, feminist and educator. Her literary work is diverse and prolific; she wrote short stories, children’s stories, journalistic texts as well as philosophical essays. In Suburg’s work the autobiographical element plays a significant role, so that we can say that throughout her whole life she wrote her own autobiography, albeit using different forms. In this article, I example specifically the autobiography written by Lilli Suburg (1841-1923 entitled Minu saatusega võitluskäik (My Fight is my Destiny (1914, with the aim of introducing the text to the modern reader and analysing its content and peculiarities. As the text was published almost a hundred years ago, it deserves to be read anew and given a fresh interpretation from a modern point of view. The text certainly adds some new aspects to understanding Lilli Suburg’s life and activity; in the article I will analyse how Suburg looks at herself and her life and the reasons why she chose to write an autobiography with a feminist emphasis. The autobiography was published in the magazine Naiste Töö ja Elu (Women’s Work and Life in 1914 and to date it is the first and only feminist autobiography in Estonia. As Suburg had been a contributor to the magazine since its foundation in 1911, it provided a forum where she was able to share her feminist ideas and worldview with the readers. The magazine’s readers were understanding and supportive of feminist ideas, and the magazine’s focus was on women’s issues and women’s interests, the contributors being the leading women of the time. In her autobiography Suburg gives an overview of her life

  19. Marss, asfaldilt maha! / Hannu Ahonen

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2010-01-01

    TM võrdleb suuri ja kalleid maastureid: Jeep Grand Cherokee 3,0 CRD TDSL V6; Land Rover Discovery 4 3,0 TDV6 HSE; Mercedes-Benz ML 350 4Matic BlueTEC Off-road Pro; Mitsubishi Pajero 3,2 DID Intense; Toyota Land Cruiser 3,0 D-4D Executive

  20. Tõlkeloo arvukad dimensioonid / Hannu K. Riikonen

    Index Scriptorium Estoniae

    Riikonen, Hannu K.

    2012-01-01

    Arvustus: Antonie Chalvin, Anne Lange, Daniele Monticelli (Eds.) Between cultures and texts : itineraries in translation history = Entre les cultures et les textes : itinéraires en histoire de la traduction. Frankfurt am Main-Berlin-Bern-Bruxelles-New York-Oxford-Wien 2011

  1. Tõlkeloo arvukad dimensioonid / Hannu K. Riikonen

    Index Scriptorium Estoniae

    Riikonen, Hannu K.

    2012-01-01

    Arvustus: Antonie Chalvin, Anne Lange, Daniele Monticelli (Eds.) Between cultures and texts : itineraries in translation history = Entre les cultures et les textes : itinéraires en histoire de la traduction. Frankfurt am Main-Berlin-Bern-Bruxelles-New York-Oxford-Wien 2011

  2. No hot, no watery, no sweet, give correct food to patients receiving chemotherapy-CSCO-Lilly medical experts' auditorium gave a speech on lung cancer in Wuhan%戒烫,戒稀,戒甜,给化疗患者正确的饮食-CSCO礼来名医大讲堂之肺癌教育在武汉行

    Institute of Scientific and Technical Information of China (English)

    Yi Cheng

    2011-01-01

    @@ The first speech of CSCO-Lilly medical experts' audi-torium in the year of 2011 was given on February 15th in Wuhan.Professor Shiying Yu, the chief of Tongji Cancer Center, and chairman of CRPC, brought a speech on "how to deal with the chemotherapy of lung cancer", which was well received by more than one hundred patients and their relatives.

  3. Klaasist looduses pole mingeid lilli / Tanel Veenre

    Index Scriptorium Estoniae

    Veenre, Tanel, 1977-

    2010-01-01

    Eesti Klaasikunstnike Ühenduse aastanäitus "Olekud" Arhitektuuri- ja Disainigaleriis 13. novembrini 2010, kuraator Eve Koha, kujundus: Laika Belka & Strelka. Aunimetuse "Tunnustatud klaasikunstnik 2008/2009" pälvis Kai Kiudsoo-Värv

  4. Väitekiri Balkani ja Baltimaade keelte evidentsiaalsusest / Hannu Tommola

    Index Scriptorium Estoniae

    Tommola, Hannu

    2010-01-01

    Arvustus: Kehayov, Petar. An areal-typological perspective to evidentiality: the cases of the Balkan and Baltic linguistic areas. Tartu : Tartu University Press, 2008. (Dissertationes linguisticae Universitatis Tartuensis ; 10)

  5. Väitekiri Balkani ja Baltimaade keelte evidentsiaalsusest / Hannu Tommola

    Index Scriptorium Estoniae

    Tommola, Hannu

    2010-01-01

    Arvustus: Kehayov, Petar. An areal-typological perspective to evidentiality: the cases of the Balkan and Baltic linguistic areas. Tartu : Tartu University Press, 2008. (Dissertationes linguisticae Universitatis Tartuensis ; 10)

  6. Moondunud tõde? / Hannu Ahonen, Velimatti Honkanen, Tapio Koisaari

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2012-01-01

    Testis kümne auto tegelikud CO₂-näidud. Bensiiniautod: Audi A5 Coupé 1,8 TFSI ; BMW 116i ; Citroën C1 1,0i ; Dacia Sandero 1,6 Hi-Flex ; Toyota Verso-S. Diiselautod: Fiat Punto 1,3 M-Jet ; Ford Mondeo 1,6 TDCi ECOnetic ; Opel Insignia Sports Tourer 2,0 CDTI EcoFlex ; Škoda Octavia HB 1,6 TDI GreenLine ; Volvo V70 1,6D DRIVe

  7. Moondunud tõde? / Hannu Ahonen, Velimatti Honkanen, Tapio Koisaari

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2012-01-01

    Testis kümne auto tegelikud CO₂-näidud. Bensiiniautod: Audi A5 Coupé 1,8 TFSI ; BMW 116i ; Citroën C1 1,0i ; Dacia Sandero 1,6 Hi-Flex ; Toyota Verso-S. Diiselautod: Fiat Punto 1,3 M-Jet ; Ford Mondeo 1,6 TDCi ECOnetic ; Opel Insignia Sports Tourer 2,0 CDTI EcoFlex ; Škoda Octavia HB 1,6 TDI GreenLine ; Volvo V70 1,6D DRIVe

  8. On aeg, mil vajame enam leiba kui lilli / Ants Juske

    Index Scriptorium Estoniae

    Juske, Ants, 1956-

    2009-01-01

    Marge Monko isikunäitus "Leib ja lilled" Tallinnas Draakoni Galeriis 21. märtsini. Eksponeeritud fotod ja video "Nora õed". Kunstnik on majanduses ja tööhõives asetleidvaid muutusi uurides aluseks võtnud Narva Kreenholmi Manufaktuuri näited

  9. On aeg, mil vajame enam leiba kui lilli / Ants Juske

    Index Scriptorium Estoniae

    Juske, Ants, 1956-

    2009-01-01

    Marge Monko isikunäitus "Leib ja lilled" Tallinnas Draakoni Galeriis 21. märtsini. Eksponeeritud fotod ja video "Nora õed". Kunstnik on majanduses ja tööhõives asetleidvaid muutusi uurides aluseks võtnud Narva Kreenholmi Manufaktuuri näited

  10. Longevidade de inflorescências de lírio, de diferentes estádios de colheita, pré-tratadas com sacarose e tiossulfato de prata (STS Longevity of lilly inflorescences harvested at different stages of development and pulsed with sucrose and silver thiosulfate (STS

    Directory of Open Access Journals (Sweden)

    José Geraldo Barbosa

    2006-02-01

    flowers at different ages. They were evaluated at length and opening of the buds, relative water content, content of chlorophyll and longevity. The longevity of lilly flowers variety Ace is influenced by the stage of harvest, with longer longevity for the younger stage, A. Inflorescences harvested at stage A and pulsed with STS had bigger diameter, but the treatment reduced the bud opening and flower quality. The sucrose improved the opening of buds harvested at stage A and increased the flower vase life. Thus the use of sucrose at 5% allowed harvesting the inflorescences at earlier stage, increasing the flower vase life.

  11. Esimene valik / Jaakko Valkiainen, Hannu Häyhä, Sampo Korhonen... [jt.

    Index Scriptorium Estoniae

    Valkiainen, Jaakko

    2014-01-01

    Seitse erineva stiili ja suurusega tsiklit algaja mootorratturi jaoks: BMW F 700 GS, Harley-Davidson XL 883 N Iron, Honda CBR 500 R, Kawasaki Ninja 300, KTM Duke 390, Suzuki GW 250 Inazuma, Yamaha FZ8-S

  12. Mõõdukad ent ruumikad : [Detroidi autonäitus NAIAS 2012] / Hannu Ahonen

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2012-01-01

    TM võrdleb universaale: Ford Focus 1,6L Wagon Trend; Kia Cee’d SW 1,6; Opel Astra Sports Tourer 1,4 Enjoy; Peugeot 308 SW Active VTi 120; Renault Mègane Grandtour 1,4 Dynamique; Volkswagen Golf Variant 1,2 TSI

  13. Esimene valik / Jaakko Valkiainen, Hannu Häyhä, Sampo Korhonen... [jt.

    Index Scriptorium Estoniae

    Valkiainen, Jaakko

    2014-01-01

    Seitse erineva stiili ja suurusega tsiklit algaja mootorratturi jaoks: BMW F 700 GS, Harley-Davidson XL 883 N Iron, Honda CBR 500 R, Kawasaki Ninja 300, KTM Duke 390, Suzuki GW 250 Inazuma, Yamaha FZ8-S

  14. Sixpack diisleid / Hannu Ahonen, Pekka Aromaa, Jari Pitkäjärvi, Isak Kullman

    Index Scriptorium Estoniae

    2008-01-01

    Diiselmootoriga mahukad pereautod: Citroën C5 2,0 Hdi Aut.; Ford Mondeo 2,0 TDCi Trend; Mazda 6 Sedan 2,0 TD Elegance; Renault Laguna 2,0 dCi Dynamique; Toyota Avensis 2,0 dt Linea Sol; Volkswagen Passat Sedan 2,0 TDI

  15. [Setomaa. Traditsioonilise arhitektuuri põhijooni ; Setomaa. Unique and genuine] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2015-01-01

    Tutvustus: Setomaa : traditsioonilise arhitektuuri põhijooni / [tekst: MTÜ Vanaajamaja ja Ahto Raudoja. [Värska] : [Seto Instituut], 2014 ; Setomaa : unique and genuine / SA Seto Instituut ; Paul Hagu jt. [Värska] : Seto Instituut, 2014

  16. Sõjas saavad alati valed mehed surma / Hannu Salonen ; intervjueerinud Margit Tõnson

    Index Scriptorium Estoniae

    Salonen, Hannu, 1972-

    2009-01-01

    Režissöör oma uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksamaa ja Iirimaa koostööfilm, kus kesksetes osades on eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  17. Sixpack diisleid / Hannu Ahonen, Pekka Aromaa, Jari Pitkäjärvi, Isak Kullman

    Index Scriptorium Estoniae

    2008-01-01

    Diiselmootoriga mahukad pereautod: Citroën C5 2,0 Hdi Aut.; Ford Mondeo 2,0 TDCi Trend; Mazda 6 Sedan 2,0 TD Elegance; Renault Laguna 2,0 dCi Dynamique; Toyota Avensis 2,0 dt Linea Sol; Volkswagen Passat Sedan 2,0 TDI

  18. Mõõdukad ent ruumikad : [Detroidi autonäitus NAIAS 2012] / Hannu Ahonen

    Index Scriptorium Estoniae

    Ahonen, Hannu

    2012-01-01

    TM võrdleb universaale: Ford Focus 1,6L Wagon Trend; Kia Cee’d SW 1,6; Opel Astra Sports Tourer 1,4 Enjoy; Peugeot 308 SW Active VTi 120; Renault Mègane Grandtour 1,4 Dynamique; Volkswagen Golf Variant 1,2 TSI

  19. Sõjas saavad alati valed mehed surma / Hannu Salonen ; intervjueerinud Margit Tõnson

    Index Scriptorium Estoniae

    Salonen, Hannu, 1972-

    2009-01-01

    Režissöör oma uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksamaa ja Iirimaa koostööfilm, kus kesksetes osades on eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  20. Pereõdede tee retseptiõiguseni kulgeb visalt / Violetta Riidas ; kommenteerinud Alar Irs, Lilli Gross

    Index Scriptorium Estoniae

    Riidas, Violetta

    2011-01-01

    Pereõdede piiratud õigus retsepte väljastada lükkub esialgu edasi. Küll aga alustavad õed farmakoloogia ja ravimikorralduse koolitusega, mida koordineerivad TÜ peremeditsiini õppetool ja farmakoloogia instituut

  1. HISTOPATHOLOGICAL STUDIES OF LIVER FUNCTION IN RATS FED ON GINGER LILLY CORM MEAL

    Directory of Open Access Journals (Sweden)

    UGWU OKECHUKWU P.C

    2013-01-01

    Full Text Available The effect of feeding Gladiolus unguiculata corm on a few liver function markers were evaluated in this study using albino Wistar rats. Twenty rats were randomly divided into four groups of five rats each. Various concentration of G. unguiculata formulations were fed to the test groups excluding the negative control which received normal feed for the 28 days of analysis. At the end of the feeding period the levels of the serum liver function markers of Aspartate aminotransferase (AST, Alanine aminotransferase (ALT, Alkaline phosphatase (ALP and Protein were determined. Mean serum liver function markers were all increased when compared with the control with only AST liver marker deviating. The ALT activity increased from 36.0 + 3.16 in the control to 38.0 + 3.16 in 20%. The AST significantly increased (p<0.05 from 66.0 + 3.16 in the 20% to 88.0 + 3.16 in the control group. ALP significantly increased from 47.0 +3.16 in the control group to 56.0 + 3.16 in 20%. Protein also increased from 7.0 +0.316 in the control group to 7.8 +0.316 in 20%. The results emanating from this study suggest that Gladiolus unguiculata corm formulations might have some deleterious effects on the liver function.

  2. Salonen: kõik tšetšeenid juba ootavad seda filmi / Hannu Salonen ; intervjueerinud Tiiu Laks

    Index Scriptorium Estoniae

    Salonen, Hannu, 1972-

    2009-01-01

    Režissöör oma uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksamaa ja Iirimaa koostööfilm, kus kesksetes osades on eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  3. Via Baltica : Eesti tee Hansaliidust Euroopa Liitu? = Via Baltica : Viron tie Hansaliitosta Euroopan Unioniin? / Hannu Eerikäinen

    Index Scriptorium Estoniae

    Eerikäinen, Hannu

    2004-01-01

    Via Baltica moodustab Läänemere regioonis tähtsaima arengutelje, mis avab Põhja-Euroopale tee EL-ist väljaspool olevatesse riikidesse. Tallinnast saab taas tähtis vahendaja Põhja- ja Kesk-Euroopa vahel

  4. Via Baltica : Eesti tee Hansaliidust Euroopa Liitu? = Via Baltica : Viron tie Hansaliitosta Euroopan Unioniin? / Hannu Eerikäinen

    Index Scriptorium Estoniae

    Eerikäinen, Hannu

    2004-01-01

    Via Baltica moodustab Läänemere regioonis tähtsaima arengutelje, mis avab Põhja-Euroopale tee EL-ist väljaspool olevatesse riikidesse. Tallinnast saab taas tähtis vahendaja Põhja- ja Kesk-Euroopa vahel

  5. Salonen: kõik tšetšeenid juba ootavad seda filmi / Hannu Salonen ; intervjueerinud Tiiu Laks

    Index Scriptorium Estoniae

    Salonen, Hannu, 1972-

    2009-01-01

    Režissöör oma uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksamaa ja Iirimaa koostööfilm, kus kesksetes osades on eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  6. V zamke otkrõlas võstavka fotografi prirodõ Finljandii

    Index Scriptorium Estoniae

    2008-01-01

    Soome loodusfotode näitus "Frozen Horizon" Narva linnuses. Oma töid näitavad Oulu läänis tegutsevad loodusfotograafid Kalervo Ojutkangas, Jorma Luhta, Hannu Hautala, Tauno Kohonen ja Hannu Huttu. Fotograafidest

  7. V zamke otkrõlas võstavka fotografi prirodõ Finljandii

    Index Scriptorium Estoniae

    2008-01-01

    Soome loodusfotode näitus "Frozen Horizon" Narva linnuses. Oma töid näitavad Oulu läänis tegutsevad loodusfotograafid Kalervo Ojutkangas, Jorma Luhta, Hannu Hautala, Tauno Kohonen ja Hannu Huttu. Fotograafidest

  8. [J. Tapio. Suljetut vaunut, eli, Kadonnutta aikaa etsimässä ; Jukka Kostiainen. Kinnises tõllas, ehk, Kadunud aega otsimas ; Tatu Vaaskivi. Maarjamaa] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2013-01-01

    Arvustus: Tapio, J. Suljetut vaunut, eli, Kadonnutta aikaa etsimässä. Porvoo : J. Kostiainen, 2012 ; Kostiainen, Jukka. Kinnises tõllas, ehk, Kadunud aega otsimas / tõlkinud Ants Paikre. Tartu : Atlex, 2013 ; Vaaskivi, Tatu. Maarjamaa / tõlkinud Ants Paikre. Tallinn : Kultuurileht, 2013. (Loomingu raamatukogu)

  9. [J. Tapio. Suljetut vaunut, eli, Kadonnutta aikaa etsimässä ; Jukka Kostiainen. Kinnises tõllas, ehk, Kadunud aega otsimas ; Tatu Vaaskivi. Maarjamaa] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2013-01-01

    Arvustus: Tapio, J. Suljetut vaunut, eli, Kadonnutta aikaa etsimässä. Porvoo : J. Kostiainen, 2012 ; Kostiainen, Jukka. Kinnises tõllas, ehk, Kadunud aega otsimas / tõlkinud Ants Paikre. Tartu : Atlex, 2013 ; Vaaskivi, Tatu. Maarjamaa / tõlkinud Ants Paikre. Tallinn : Kultuurileht, 2013. (Loomingu raamatukogu)

  10. Estonia halts expansion of "expensive" windmills / Kairi Kurm

    Index Scriptorium Estoniae

    Kurm, Kairi

    2005-01-01

    Majandus- ja kommunikatsiooniministeeriumi osakonnajuhataja Einari Kisel ja AS-i Tuulepargid tegevdirektor Hannu Lamp tuuleenergia tootmisest Eestis. Tabelid: Iga-aastane tuuleenergia tootmine Euroopa Liidus; Planeeritud tuuleenergia tootmine

  11. Estonia halts expansion of "expensive" windmills / Kairi Kurm

    Index Scriptorium Estoniae

    Kurm, Kairi

    2005-01-01

    Majandus- ja kommunikatsiooniministeeriumi osakonnajuhataja Einari Kisel ja AS-i Tuulepargid tegevdirektor Hannu Lamp tuuleenergia tootmisest Eestis. Tabelid: Iga-aastane tuuleenergia tootmine Euroopa Liidus; Planeeritud tuuleenergia tootmine

  12. [Uue Eesti loojad. Uuden Viron luojat : välähdyksiä Tampereen Rudolf Steiner-koulun viro-kummiryhmän toiminnasta 1989-1999 ; Varsinais-Suomi ja Viro : Varsinais-Suomen Virokeskus 20 vuotta] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2015-01-01

    Arvustus: Uue Eesti loojad. Uuden Viron loojat / toimetaja Liisa Niinikangas. Jyväskylä : Lighthouse Consulting, 2014 ; Varsinais-Suomi ja Viro : Varsinais-Suomen Virokeskus 20 vuotta / toimetajad Veikko Laakso ja Kirsi Äyräs. [Turku] : Varsinais-Suomen Viro-keskus, 2015

  13. [Uue Eesti loojad. Uuden Viron luojat : välähdyksiä Tampereen Rudolf Steiner-koulun viro-kummiryhmän toiminnasta 1989-1999 ; Varsinais-Suomi ja Viro : Varsinais-Suomen Virokeskus 20 vuotta] / Hannu Oittinen

    Index Scriptorium Estoniae

    Oittinen, Hannu, 1959-

    2015-01-01

    Arvustus: Uue Eesti loojad. Uuden Viron loojat / toimetaja Liisa Niinikangas. Jyväskylä : Lighthouse Consulting, 2014 ; Varsinais-Suomi ja Viro : Varsinais-Suomen Virokeskus 20 vuotta / toimetajad Veikko Laakso ja Kirsi Äyräs. [Turku] : Varsinais-Suomen Viro-keskus, 2015

  14. 77 FR 46612 - New Animal Drugs; Change of Sponsor; Change of Sponsor Address; Azaperone; Miconazole, Polymyxin...

    Science.gov (United States)

    2012-08-06

    ... applications (NADAs) from Janssen Pharmaceutica NV, to Elanco Animal Health, a Division of Eli Lilly & Co. FDA... Animal Health, a Division of Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285....

  15. Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

    OpenAIRE

    Anand E; Berggren L; Landry J; Tóth Á; Detke HC

    2016-01-01

    Ernie Anand,1 Lovisa Berggren,2 John Landry,3 Ágoston Tóth,4 Holland C Detke5 1Neuroscience Medical Affairs, Eli Lilly & Company Ltd, Windlesham, UK; 2Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany; 3Global Statistical Sciences, Eli Lilly Canada Inc., Toronto, ON, Canada; 4Neuroscience, Lilly Hungary, Budapest, Hungary; 5Psychiatry and Pain Disorders, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Background...

  16. Raamatureisid Veneetsiasse / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2005-01-01

    Arvustus: Girardi, Robert. Vaporetto 13 / ingl. k. tlk. Karin Suursalu. Tallinn : Kultuurileht, 2005. (Loomingu Raamatukogu) ; Raittila, Hannu. Canal Grande : [romaan] / tõlkinud Aivo Lõhmus. Tallinn : Varrak, 2003 (Moodne aeg)

  17. Liina Tennosaar : "Enda meelest olen ilus vanainimene" / Liina Tennosaar ; interv. Jaanus Kulli

    Index Scriptorium Estoniae

    Tennosaar, Liina

    2008-01-01

    Näitlejanna endast ja osalemisest Hannu Saloneni käe all valmivas Eesti-Soome-Saksamaa koostööfilmis "Kid & Killer". Lisaks "Epp Pillarpart andis Liina lapsele nime" ja meenutus "Teismeline soovis surmapurjekal seilata"

  18. Maksupolitsei süüdistab tuntud moekunstnikku maksukuriteos / Marko Püüa

    Index Scriptorium Estoniae

    Püüa, Marko

    2003-01-01

    Maksupettuste uurimise keskuse süüdistustest moekunstnik Ülle Suurhans-Pohjanheimo ja tema abikaasa Hannu Tapani Pohjanheimo vastu, kes juhtisid 2001. aastal kodutehnika ekspordi ja impordiga tegelevat osaühingut Eespert. Lisa: 203 kuriteoepisoodi

  19. Lugemisnoppeid / Toomas Tiivel

    Index Scriptorium Estoniae

    Tiivel, Toomas, 1952-

    2012-01-01

    Tutvustus: Tarand, Andres, Strandberg, Marek. Rahvusliku julgeoleku küsimus : Andres Tarandi ja Marek Strandbergi kriitilised kõned Eesti energeetika arengu asjus. Tallinn, 2010 ; Lauerma, Hannu. Usk, lootus ja ohtlik bluff : julgustamisest vaimse terrorini. Tallinn, 2008

  20. Liina Tennosaar : "Enda meelest olen ilus vanainimene" / Liina Tennosaar ; interv. Jaanus Kulli

    Index Scriptorium Estoniae

    Tennosaar, Liina

    2008-01-01

    Näitlejanna endast ja osalemisest Hannu Saloneni käe all valmivas Eesti-Soome-Saksamaa koostööfilmis "Kid & Killer". Lisaks "Epp Pillarpart andis Liina lapsele nime" ja meenutus "Teismeline soovis surmapurjekal seilata"

  1. Raamatureisid Veneetsiasse / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2005-01-01

    Arvustus: Girardi, Robert. Vaporetto 13 / ingl. k. tlk. Karin Suursalu. Tallinn : Kultuurileht, 2005. (Loomingu Raamatukogu) ; Raittila, Hannu. Canal Grande : [romaan] / tõlkinud Aivo Lõhmus. Tallinn : Varrak, 2003 (Moodne aeg)

  2. Rauno Pukonen : Meie toodangut armastatakse, meid endid mitte / Rauno Pukonen ; interv. Svea Talving

    Index Scriptorium Estoniae

    Pukonen, Rauno

    2004-01-01

    Farmaatsiafirmast Eli Lilly, ravimifirmade madalast mainest. Eli Lilly filiaali juhi sõnul ei lase väike turg ja tagasihoidlik kompensatsioon võimalikku ravimivalikut Eestisse tuua. Lisa: Fakte ettevõttest

  3. 75 FR 5887 - New Animal Drugs for Use in Animal Feeds; Ractopamine; Monensin

    Science.gov (United States)

    2010-02-05

    ... new animal drug application (NADA) filed by Elanco Animal Health, A Division of Eli Lilly & Co. The NADA provides for use of single-ingredient Type A medicated articles containing ractopamine..., A Division of Eli Lilly ] & Co., Lilly Corporate Center, Indianapolis, IN 46285, filed NADA 141-...

  4. Vasha paugutab püstolit päriselus nagu filmis / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2009-01-01

    Võrdlus Hannu Saloneni Eesti, Soome, Saksa ja Iiri koostööfilmis "Vasha" toimunu ja tegelike sündmustega tšetšeeni emigrantide hulgas. Tegelik elu on traagilisem ja dünaamilisem kui mängufilmis näidatu

  5. 20 miljoni eest põnevust / Piret Tibbo-Hudgins

    Index Scriptorium Estoniae

    Tibbo-Hudgins, Piret

    2009-01-01

    Produtsent Eesti-Saksa-Soome-Iirimaa koostööfilmist "Vasha", kus osalevad Eesti näitlejad ning filmitegijad Saksamaalt, Soomest ja Iirimaalt. Filmi režissöör on Hannu Salonen, peategelased Mart Müürisepp ja Mehmet Kurtulus

  6. Suur müüdikonverents Tartus / Evelin Banhard

    Index Scriptorium Estoniae

    Banhard, Evelin

    2008-01-01

    Tartus toimunud rahvusvahelisest konverentsist "Suurte kultuuriliste ja kirjanduslike müütide saatus tänapäeval". Pikemalt Liisa Saariluoma, Jüri Talveti, Angelika Stefanova, Tanel Lepsoo, Caroline De Wagteri, Sonia Bravo Utrera, Ana Martinoska, Marin Laagi, Rutt Hinrikuse, Jeanne Elisabeth Gleseneri, Sabine Coelsch-Foisneri, Harvey L. Hixi ja Hannu K. Riikoneni ettekannetest

  7. Suur müüdikonverents Tartus / Evelin Banhard

    Index Scriptorium Estoniae

    Banhard, Evelin

    2008-01-01

    Tartus toimunud rahvusvahelisest konverentsist "Suurte kultuuriliste ja kirjanduslike müütide saatus tänapäeval". Pikemalt Liisa Saariluoma, Jüri Talveti, Angelika Stefanova, Tanel Lepsoo, Caroline De Wagteri, Sonia Bravo Utrera, Ana Martinoska, Marin Laagi, Rutt Hinrikuse, Jeanne Elisabeth Gleseneri, Sabine Coelsch-Foisneri, Harvey L. Hixi ja Hannu K. Riikoneni ettekannetest

  8. Pärnu ja Viljandi on taas aktide päralt, seekord liikuvate / Siram

    Index Scriptorium Estoniae

    Siram, pseud., 1968-

    2009-01-01

    XVI rahvusvaheline aktinäitus "Mees ja naine" 30. augustini Uue Kunsti Muuseumis Pärnus ja Viljandis, kuraator Mark Soosaar. Pikemalt valgevene kunstniku Ruslan Vaškevitši ja soomlase Hannu Riikoneni töödest

  9. Vasha paugutab püstolit päriselus nagu filmis / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2009-01-01

    Võrdlus Hannu Saloneni Eesti, Soome, Saksa ja Iiri koostööfilmis "Vasha" toimunu ja tegelike sündmustega tšetšeeni emigrantide hulgas. Tegelik elu on traagilisem ja dünaamilisem kui mängufilmis näidatu

  10. "Vasha" on mitme lõpuga film / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    Hannu Saloneni uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksa ja Iiri koostööfilmist, kus kesksetes osades on türklane Mehmet Kurtulus, eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  11. 20 miljoni eest põnevust / Piret Tibbo-Hudgins

    Index Scriptorium Estoniae

    Tibbo-Hudgins, Piret

    2009-01-01

    Produtsent Eesti-Saksa-Soome-Iirimaa koostööfilmist "Vasha", kus osalevad Eesti näitlejad ning filmitegijad Saksamaalt, Soomest ja Iirimaalt. Filmi režissöör on Hannu Salonen, peategelased Mart Müürisepp ja Mehmet Kurtulus

  12. Viikki kool : Kevätkatu 2, Helsingi = Viikki Teacher Training School

    Index Scriptorium Estoniae

    2004-01-01

    Viiki uus kool toimib Helsingi Ülikooli pedagoogikaosakonna praktikakoolina, siin on nii põhi- kui keskkooliõpe. Raudbetoonelementidest hoone, fassaadid on põhiliselt valged betoonist sandwich-paneelid. Projekteerija: ARK-house Arkkitehdit. Autorid Markku Erholtz, Hannu Huttunen, Jussi Karjalainen. Valmis 2001. 5 välis- ja 7 sisevaadet

  13. Viikki kool : Kevätkatu 2, Helsingi = Viikki Teacher Training School

    Index Scriptorium Estoniae

    2004-01-01

    Viiki uus kool toimib Helsingi Ülikooli pedagoogikaosakonna praktikakoolina, siin on nii põhi- kui keskkooliõpe. Raudbetoonelementidest hoone, fassaadid on põhiliselt valged betoonist sandwich-paneelid. Projekteerija: ARK-house Arkkitehdit. Autorid Markku Erholtz, Hannu Huttunen, Jussi Karjalainen. Valmis 2001. 5 välis- ja 7 sisevaadet

  14. "Vasha" on mitme lõpuga film / Tiiu Laks

    Index Scriptorium Estoniae

    Laks, Tiiu, 1984-

    2009-01-01

    Hannu Saloneni uuest mängufilmist "Vasha" (endine tööpealkiri "Kid ja Killer"), Eesti, Soome, Saksa ja Iiri koostööfilmist, kus kesksetes osades on türklane Mehmet Kurtulus, eestlastest Mart Müürisepp, Rein Oja, Jan Uuspõld jt

  15. Uue mängufilmi võtted / E. K.

    Index Scriptorium Estoniae

    E. K.

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins)

  16. Varem olin ma mänginud kooliteatris vaid puud / Jaanus Kulli

    Index Scriptorium Estoniae

    Kulli, Jaanus, 1955-

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör ja üks stsenariste Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, peaprodutsent Piret Tibbo-Hudgins). Ühte peaossa valiti Westholmi gümnaasiumi õpilane Mart Müürisepp

  17. Viru keskuses plahvatab mitu päeva järjest / Ants Vill

    Index Scriptorium Estoniae

    Vill, Ants, 1955-

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins). 24-25. märtsil filmitakse Viru Keskuses

  18. Eesti luule Kajaani sõnakunsti päevadel / Endel Mallene

    Index Scriptorium Estoniae

    Mallene, Endel, 1933-2002

    1996-01-01

    Ülevaade Kajaani sõnakunsti päevadest 'Sõna ja heli' ('Sana ja sävel'), kus toimus ka eesti kirjanike luuleõhtu ja Sass Suumani valikkogu esitlus: Suuman, Sass. Viisaampaa ei ole / Tlk. Pirkko Huurto, Ritva Hyry, Hannu Oittinen. Saarijärvi : Pohjoinen, 1996

  19. Mechatronics Design of an Unmanned Ground Vehicle for Military Applications

    OpenAIRE

    Appelqvist, Pekka; Knuuttila, Jere; Ahtiainen, Juhana

    2010-01-01

    Our research was funded by the Finnish Defence Forces' technology program and additionally by the Scientific Advisory Board for Defence. The authors also want to thank other project partners, especially Patria Group and VTT (Dr. Hannu Lehtinen, Dr. Ilkka Kauppi, Petri Kaarmila and Jarmo Prokkola).

  20. Varem olin ma mänginud kooliteatris vaid puud / Jaanus Kulli

    Index Scriptorium Estoniae

    Kulli, Jaanus, 1955-

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör ja üks stsenariste Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, peaprodutsent Piret Tibbo-Hudgins). Ühte peaossa valiti Westholmi gümnaasiumi õpilane Mart Müürisepp

  1. Viru keskuses plahvatab mitu päeva järjest / Ants Vill

    Index Scriptorium Estoniae

    Vill, Ants, 1955-

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins). 24-25. märtsil filmitakse Viru Keskuses

  2. Uue mängufilmi võtted / E. K.

    Index Scriptorium Estoniae

    E. K.

    2008-01-01

    Allfilm koos Saksa, Soome ja Iiri partneritega alustas Tallinnas action-mängufilmi "Kid & Killer" võtteid (režissöör Hannu Salonen, stsenaristid Mart Kivastik ja Katrin Laur, operaator Rein Kotov, produtsent Piret Tibbo-Hudgins)

  3. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A

    OpenAIRE

    Liu, Ling; Kikly, Kristine; Lu, Jirong; Allan,Barrett; Tang, Ying; Tetreault,Jonathan; Chow,Chi-Kin; Barmettler,Barbara; Nelson, James; Bina,Holly; HUANG, LIHUA; Wroblewski, Victor

    2016-01-01

    Ling Liu,1 Jirong Lu,1 Barrett W Allan,2 Ying Tang,2 Jonathan Tetreault,1 Chi-kin Chow,1 Barbra Barmettler,2 James Nelson,2 Holly Bina,1 Lihua Huang,3 Victor J Wroblewski,4 Kristine Kikly1 1Biotechnology Discovery Research, Indianapolis, IN, 2Applied Molecular Evolution, Lilly Biotechnology Center, San Diego, CA, 3Bioproduct Research and Development, 4Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: Interleukin (IL)-17A exists as a...

  4. Ravimikontsern võitis soodusravimitülis kohtus sotsiaalministeeriumi / Signe Kalberg

    Index Scriptorium Estoniae

    Kalberg, Signe, 1959-

    2007-01-01

    Tallinna halduskohtu otsusest rahvusvahelise farmaatsiakontserni Eli Lilly ja sotsiaalministeeriumi vahelises kohtuasjas aktiivsus- ja tähelepanuhäiretega lastele mõeldud ravimi soodustuse taotlumise kohta

  5. 'Szhigaja eti kulturnõje mostõ...' : Moskva-Tallinn 1958-1986 / Vera Ruber

    Index Scriptorium Estoniae

    Ruber, Vera, 1925-2011

    1997-01-01

    Tööst eesti kirjanduse konsultandina Üleliidulise Kirjanike Liidu juhatusse sekretariaadis. Ka 1959. a. romaanivõistlusel silmapaistnud romaanidest (Lilli Prometi 'Meesteta küla' ja Raimond Kaugveri 'Võõra mõõga teenistuses'), Lilli Prometi romaanist 'Primavera' ja venekeelsest kogumikust 'Eesti noor proosa' (1978)

  6. Ainult 1%-meestest ei ole erektsioonihäire ravitav

    Index Scriptorium Estoniae

    2004-01-01

    Erektsioonihäirete põhjustest, seotud haigustest ja ravimeetoditest rääkisid ravimifirma Eli Lilly korraldatud loengupäeval uroloog Margus Punab, kardioloog Arvo Rosenthal, psühhiaater Imre Rammul ja Eli Lilly turundusjuht Katrin Lätt

  7. Rauno Pukonen : Turule tulevad vaid oma klassi parimad rohud / Rauno Pukonen ; interv. Vilve Torn

    Index Scriptorium Estoniae

    Pukonen, Rauno

    2006-01-01

    Rahvusvahelise Ravimitootjate Liidu juhatuse esimees ja Eli Lilly Balti regiooni direktor vastab küsimustele, mis puudutavad innovatiivsusest ja kvaliteedist lähtumise põhimõtet ravimitootmises, ravimihindade teket, firma 70 miljoni dollari suurust toetust tuberkuloosiprogrammile, firma tulevikku. Lisad: Eli Lilly & Co 130; Ajalugu

  8. Atomoxetine Open-Label Trial in ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2002-07-01

    Full Text Available Atomoxetine (originally named tomoxetine, a new therapy for attention deficit hyperactivity disorder (ADHD marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories.

  9. 76 FR 12563 - Oral Dosage Form New Animal Drugs; Spinosad and Milbemycin Oxime

    Science.gov (United States)

    2011-03-08

    ... animal drug application (NADA) filed by Elanco Animal Health. The NADA provides for veterinary... Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285, filed NADA 141-321 that provides for... parasites. The NADA is approved as of January 4, 2011, and the regulations in part 520 (21 CFR part 520)...

  10. 'Szhigaja eti kulturnõje mostõ...' : Moskva-Tallinn 1958-1986 / Vera Ruber

    Index Scriptorium Estoniae

    Ruber, Vera, 1925-2011

    1997-01-01

    Tööst eesti kirjanduse konsultandina Üleliidulise Kirjanike Liidu juhatusse sekretariaadis. Ka 1959. a. romaanivõistlusel silmapaistnud romaanidest (Lilli Prometi 'Meesteta küla' ja Raimond Kaugveri 'Võõra mõõga teenistuses'), Lilli Prometi romaanist 'Primavera' ja venekeelsest kogumikust 'Eesti noor proosa' (1978)

  11. Health advocacy organizations and the pharmaceutical industry: an analysis of disclosure practices.

    Science.gov (United States)

    Rothman, Sheila M; Raveis, Victoria H; Friedman, Anne; Rothman, David J

    2011-04-01

    Health advocacy organizations (HAOs) are influential stakeholders in health policy. Although their advocacy tends to closely correspond with the pharmaceutical industry's marketing aims, the financial relationships between HAOs and the pharmaceutical industry have rarely been analyzed. We used Eli Lilly and Company's grant registry to examine its grant-giving policies. We also examined HAO Web sites to determine their grant-disclosure patterns. Only 25% of HAOs that received Lilly grants acknowledged Lilly's contributions on their Web sites, and only 10% acknowledged Lilly as a grant event sponsor. No HAO disclosed the exact amount of a Lilly grant. As highly trusted organizations, HAOs should disclose all corporate grants, including the purpose and the amount. Absent this disclosure, legislators, regulators, and the public cannot evaluate possible conflicts of interest or biases in HAO advocacy.

  12. Disain - argipäeva polster / Karin Paulus

    Index Scriptorium Estoniae

    Paulus, Karin, 1975-

    2005-01-01

    2005. a. aprillis Tallinnas Disaini- ja Arhitektuurigaleriis eksponeeritud 2005. a. Fennia Prize rahvusvahelisel konkursil auhinnatud tööstuskunsti väljapanekust ja seminarist. Peapreemia - firma Lappset mänguväljakukomplekt "Axiom" (disainerid Hannu Ylinenpää, Marjo Naukkarinen, Esa Junttila). Mööbli osas märgiti ära Päivi Mikola kavandatud kiiktool "Woodpecker"

  13. Neuroscience-Enabled Complex Visual Scene Understanding

    Science.gov (United States)

    2012-04-12

    34, Rivista di Psicologia 49 (1): 7–30 • Kauppinen, Hannu. Seppanen, Tapio and Pietikainen, Matti. An Experimental Comparison of Autoregressive and...a Social Robot,“ IJCAI, pp. 1146-1151, 1999. [63] G. Heidemann, R. Rae, H. Bekel, I. Bax, and H. Ritter, ”Inte- grating Context-free and Context... social interaction. In Interna- tional Conference on Robotics, Automation, and Mecha- tronics (RAM 2006), Bangkok Thailand. Se, S., Lowe, D. G

  14. Bagatellid : maailm / Nele-Eva Steinfeld, Ivo Heinloo

    Index Scriptorium Estoniae

    Steinfeld, Nele-Eva

    2011-01-01

    Muusikasõnumeid maailmast: Jiri Belohlavek naaseb Tšehhi filharmoonia peadirigendiks. Alfred Brendel 80. Sir Simon Rattle'i debüüt Metropolitan Operas. Soome raadio sümfooniaorkestri peadirigendiks saabHannu Lintu. 2012. aasta Viini uusaastakontserti juhatab Maris Jansons. Uus täht jazzitaevas - Christian Scott. Valik uusi jazziraamatuid. Itaalia muusikaajakiri Musica Jazz valis aasta parimaid jazzmuusikuid. Grammy võitjad selgunud. Michael Jackson jätkab postuumselt müügirekordite purustamist

  15. Bagatellid : maailm / Nele-Eva Steinfeld, Ivo Heinloo

    Index Scriptorium Estoniae

    Steinfeld, Nele-Eva

    2011-01-01

    Muusikasõnumeid maailmast: Jiri Belohlavek naaseb Tšehhi filharmoonia peadirigendiks. Alfred Brendel 80. Sir Simon Rattle'i debüüt Metropolitan Operas. Soome raadio sümfooniaorkestri peadirigendiks saabHannu Lintu. 2012. aasta Viini uusaastakontserti juhatab Maris Jansons. Uus täht jazzitaevas - Christian Scott. Valik uusi jazziraamatuid. Itaalia muusikaajakiri Musica Jazz valis aasta parimaid jazzmuusikuid. Grammy võitjad selgunud. Michael Jackson jätkab postuumselt müügirekordite purustamist

  16. Terrorism, pommid ja pangarööv / Anari Koppel

    Index Scriptorium Estoniae

    Koppel, Anari

    2008-01-01

    Töös olevad Eesti mängufilmid - "Kid&Killer" (produtsent Piret Tibbo Hudgins, stsenaristid Mart Kivastik, Katrin Laur ja Hannu Salonen, kes ka filmi lavastab), "Külaline" (soome, saksa eesti, inglise koostööfilm, lavastaja Jukka-Pekka Valkeapää, operaator Tuomo Hutri, produtsent Marit Ahven), "Pangarööv" (režissöör Andrus Tuisk, stsenarist Mihkel Ulman, produtsent Manfred Vainokivi)

  17. Terrorism, pommid ja pangarööv / Anari Koppel

    Index Scriptorium Estoniae

    Koppel, Anari

    2008-01-01

    Töös olevad Eesti mängufilmid - "Kid&Killer" (produtsent Piret Tibbo Hudgins, stsenaristid Mart Kivastik, Katrin Laur ja Hannu Salonen, kes ka filmi lavastab), "Külaline" (soome, saksa eesti, inglise koostööfilm, lavastaja Jukka-Pekka Valkeapää, operaator Tuomo Hutri, produtsent Marit Ahven), "Pangarööv" (režissöör Andrus Tuisk, stsenarist Mihkel Ulman, produtsent Manfred Vainokivi)

  18. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A

    OpenAIRE

    Liu L; Lu J; Allan BW; Tang Y.; Tetreault J; Chow C; Barmettler B; Nelson J; Bina H; Huang L; Wroblewski VJ; Kikly K

    2016-01-01

    Ling Liu,1 Jirong Lu,1 Barrett W Allan,2 Ying Tang,2 Jonathan Tetreault,1 Chi-kin Chow,1 Barbra Barmettler,2 James Nelson,2 Holly Bina,1 Lihua Huang,3 Victor J Wroblewski,4 Kristine Kikly1 1Biotechnology Discovery Research, Indianapolis, IN, 2Applied Molecular Evolution, Lilly Biotechnology Center, San Diego, CA, 3Bioproduct Research and Development, 4Drug Disposition, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: Interleukin (IL)-17A exists as a hom...

  19. Suvine briis rõduaias / Toomas Türk

    Index Scriptorium Estoniae

    Türk, Toomas

    2004-01-01

    Barry Mayledi kujundatud meremeeleoludes rõduaed Chelsea 2003. a. lillenäitusel. Plastiktoolid meenutavad merelaineid, põrandakatteks on keeratud köis, taimedeks valitud peamiselt madalakasvulisi lilli. 2 ill

  20. Nava talu laulab piirid avatuks

    Index Scriptorium Estoniae

    2008-01-01

    Nava talu eestvõttel leiab 23. veebruaril Karksi vallas Lilli külas aset üritus, kus Läti-Eesti piir avatuks lauldakse. Nava talu peremees Jaak Kõdar ka teistest Nava taluga seotud ettevõtmistest

  1. Prevalence and correlates of atypical patterns of drug use progression

    African Journals Online (AJOL)

    used a) alcohol, b) tobacco, c) cannabis, d) other drugs. (including drugs such as cocaine, ...... the John D. and Catherine T. MacArthur Foundation, the. Pfizer Foundation, the US ... American Health Organization, Eli Lilly and Company, Ortho-.

  2. Browse Title Index

    African Journals Online (AJOL)

    Items 1 - 50 of 317 ... Working with Groups by Lilly Becker (ed.) Abstract ... Ciara Wynne, Caoimhe Doyle, Rachel Kenny, Eileen Brosnan, John Sharry ... Karmel W. Choi, Melissa H. Watt, Donald Skinner, Seth C. Kalichman, Kathleen J. Sikkema.

  3. Korp! Filiae Patriae 85. aastapäeva pidustused Los Angeleses / Lumme Erilt

    Index Scriptorium Estoniae

    Erilt, Lumme

    2005-01-01

    5. novembril 2005 tähistas Filiae Patriae Kalifornia koondis Los Angelese Eesti Majas piduliku õestuspeo ning ühise perekonnaõhtuga koos korp! Rotaliaga aastapäeva. Peeti kõnesid, oli tervitusi, muusikat, palju lilli

  4. Naised mõrvarite jälil / Kaisa Karu

    Index Scriptorium Estoniae

    Karu, Kaisa

    2010-01-01

    Kanal 2 ekraanil kaks naispeaosalistega krimisarja : uurija Lilly Rush (Kathryn Morris) sarjas "Jahtunud jälg" (USA, 2003-... ) ja Brenda Leigh Johnson (Kyra Sedgwick) seriaalis "Vahelevõtja" (USA, 2005-... )

  5. Naised mõrvarite jälil / Kaisa Karu

    Index Scriptorium Estoniae

    Karu, Kaisa

    2010-01-01

    Kanal 2 ekraanil kaks naispeaosalistega krimisarja : uurija Lilly Rush (Kathryn Morris) sarjas "Jahtunud jälg" (USA, 2003-... ) ja Brenda Leigh Johnson (Kyra Sedgwick) seriaalis "Vahelevõtja" (USA, 2005-... )

  6. Moodne nädal Tallinnas

    Index Scriptorium Estoniae

    2007-01-01

    Moenädala FIBIT (Fashion Is Back In Tallinn) Viru Keskuses ja Kristiine Keskuses 8.03.-11.03.2007. Kristiine Keskuses tutuvustatakse Gerly Tinni, Jevgeni Fokini ja Lilli Jahilo loomingut, etenduste lavastaja Helen Sirp

  7. Täiskasvanud õppija nädal 2010 / Reet Saar

    Index Scriptorium Estoniae

    Saar, Reet, 1959-

    2010-01-01

    Raplamaa Aasta õppija on Märjamaa perearstikeskuse õde Ljudmilla Tamp, Aasta koolitaja tantsuõpetaja Lilli Teesalu, Aasta koolitussõbralikum organisatsioon on Kehtna põhikool ja aasta koolitussõbralikum omavalitsus Kohila vald

  8. Korp! Filiae Patriae 85. aastapäeva pidustused Los Angeleses / Lumme Erilt

    Index Scriptorium Estoniae

    Erilt, Lumme

    2005-01-01

    5. novembril 2005 tähistas Filiae Patriae Kalifornia koondis Los Angelese Eesti Majas piduliku õestuspeo ning ühise perekonnaõhtuga koos korp! Rotaliaga aastapäeva. Peeti kõnesid, oli tervitusi, muusikat, palju lilli

  9. [Lahkunud 2007

    Index Scriptorium Estoniae

    2007-01-01

    2007. a. lahkunud kirjanikud, kirjandusteadlased ja tõlkijad: Silvia Rannamaa, Debora Vaarandi, Arvo Alas, Juhan Peegel, Jaan Kross, Lilli Promet, Ilmar Talve, Juhan Saar, Vello Lattik, Oskar Kruus, Norman Mailer, Kurt Vonnegut, Henri Troyat

  10. Важнейшим из искусств для нас является мода / Лиана Турпакова ; комментировала Ирина Свидлов

    Index Scriptorium Estoniae

    Турпакова, Лиана

    2009-01-01

    Tallinna 3. moenädalal esitletud moekollektsioonidest: Katrin Kuldma "Amanjeda", Oksana Tanditi "Never Hide", Lilli Jahilo ja Kristina Viirpalu talvekollektsioon, Diana Denissova "Uus barokk". Katrin Kuldma kollektsiooni kommenteerib Irina Svidlov. Vaata ka lk. 58-59

  11. Presidential Green Chemistry Challenge: 1999 Greener Synthetic Pathways Award

    Science.gov (United States)

    Presidential Green Chemistry Challenge 1999 award winner, Lilly Research Laboratories, developed a low-waste drug synthesis using yeast for a stereospecific reduction, reducing solvent amounts, and replacing chromium oxide.

  12. Täiskasvanud õppija nädal 2010 / Reet Saar

    Index Scriptorium Estoniae

    Saar, Reet, 1959-

    2010-01-01

    Raplamaa Aasta õppija on Märjamaa perearstikeskuse õde Ljudmilla Tamp, Aasta koolitaja tantsuõpetaja Lilli Teesalu, Aasta koolitussõbralikum organisatsioon on Kehtna põhikool ja aasta koolitussõbralikum omavalitsus Kohila vald

  13. Важнейшим из искусств для нас является мода / Лиана Турпакова ; комментировала Ирина Свидлов

    Index Scriptorium Estoniae

    Турпакова, Лиана

    2009-01-01

    Tallinna 3. moenädalal esitletud moekollektsioonidest: Katrin Kuldma "Amanjeda", Oksana Tanditi "Never Hide", Lilli Jahilo ja Kristina Viirpalu talvekollektsioon, Diana Denissova "Uus barokk". Katrin Kuldma kollektsiooni kommenteerib Irina Svidlov. Vaata ka lk. 58-59

  14. Külma oru peremees / Airi Hallik

    Index Scriptorium Estoniae

    Hallik, Airi, 1975-

    2007-01-01

    Vanu talutraditsioone elus hoidvate metsandusspetsialistide Jaak ja Mall Põldma Sõrmuse talust Karksi vallas Lilli külas. 1903. a. valminud rehielamust. 1879. a. ehitatud aidas hoitakse vanavara. Ill.: 10 värv. vaadet

  15. Mõnda Eesti kirjanduselust Moskva vaatevinklist (1958-1986) : [mälestusi ja päevikumärkmeid aastaist 1968-1969] / Vera Ruber

    Index Scriptorium Estoniae

    Ruber, Vera, 1925-2011

    1997-01-01

    Tööst eesti kirjanduse konsultandina Üleliidulise Kirjanike Liidu juhatuse sekretariaadis. Ka 1959. a. romaanivõistlusel silmapaistnud romaanidest (Lilli Prometi "Meesteta küla" ja Raimond Kaugveri "Võõra mõõga teenistuses"), Lilli Prometi romaanist "Primavera" ja venekeelsest kogumikust "Eesti noor proosa" ("Эстонская молодая проза", koost. Endel Mallene ja Rein Saluri, 1978)

  16. The Battle of the Narrative

    Science.gov (United States)

    2010-04-06

    Gibraltar in 1993. 80The King of Hedjaz and Arab Independence, (London: Hayman, Christy and Lilly , 1917), 12. 33 Only nine months earlier on March 19...Conflict after the Cold War: Arguments on Causes of War and Peace . Columbia University: Longman, 2002. Bucktin, Chris. “Hello to All That.” In...Hedjaz and Arab Independence. London: Hayman, Christy and Lilly , 1917. 55 Kingdon, John W. Agendas, Alternatives, and Public Policies. Boston

  17. Centers of Stability Analysis - The Missing Framework in Joint Intelligence Preparation of the Operational Environment Doctrine

    Science.gov (United States)

    2011-05-04

    assessment of the 17 Douglas D. Lilly , “Strategic Framing of Stability Operations” (research paper...inaccurate if the operation is in phase zero or four, as the objectives should be focused on stability or peace operations. The concepts used in COG...War." Research report, Maxwell Air Force Base, AL: U.S. Air University, 1988. Lilly , Douglas D. “Strategic Framing of Stability Operations

  18. Organizational Implications of the U.S. Army’s Increasing Demand for Explosive Ordnance Disposal Capabilities

    Science.gov (United States)

    2008-05-22

    5. 39 Anne Chapman, Benjamin King, and Carol Lilly, Transforming the Army. TRADOC’s First Thirty Years: 1973-2003 (Fort Monroe, VA: Military...Unexploded Ordnance (UXO),“ http://www.globalsecurity.org/ military/ systems/munitions /uxo.htm (accessed 20 March 2008) 73 Captain Catherine A. Reese ...14 April 2004. Chapman, Ann, King, Benjamin, and Lilly, Carol . Transforming the Army. TRADOC’s First Thirty Years: 1973-2003. Fort Monroe, VA

  19. Mõnda Eesti kirjanduselust Moskva vaatevinklist (1958-1986) : [mälestusi ja päevikumärkmeid aastaist 1968-1969] / Vera Ruber

    Index Scriptorium Estoniae

    Ruber, Vera, 1925-2011

    1997-01-01

    Tööst eesti kirjanduse konsultandina Üleliidulise Kirjanike Liidu juhatuse sekretariaadis. Ka 1959. a. romaanivõistlusel silmapaistnud romaanidest (Lilli Prometi "Meesteta küla" ja Raimond Kaugveri "Võõra mõõga teenistuses"), Lilli Prometi romaanist "Primavera" ja venekeelsest kogumikust "Eesti noor proosa" ("Эстонская молодая проза", koost. Endel Mallene ja Rein Saluri, 1978)

  20. IBBY Eesti osakond 2007

    Index Scriptorium Estoniae

    2007-01-01

    IBBY Eesti osakond esitas Astrid Lindgreni mälestusauhinna kandidaatideks kirjanik Aino Perviku, illustraatorid Regina Lukk-Toompere ja Ilon Wiklandi. Paabeli Torni auhinna pälvis Arvo Valton komi kirjaniku Vladimir Timini noorsooromaani "Vana-Permi poisi Tikö seiklused" eesti keelde tõlkimise eest. IBBY aunimekirja esitati A. Kivirähk raamatuga "Leiutajateküla Lotte", kunstnik Jüri Mildeberg illustratsioonidega raamatule "Ruttu tuttu" ja tõlkija Piret Saluri Hannu Mäkela raamatu "Härra Huu teeb aiatööd" tõlkimise eest

  1. Lutikat : [luuletused] / Viktor Shibanov

    Index Scriptorium Estoniae

    Shibanov, Viktor

    2005-01-01

    Sisu: Lutikat / udmurdi keelest soome keelde tõlkinud Viktor Shibanov, Sara Hännikäinen ; Ylösalaisin kasvava puu / udmurdi keelest soome keelde tõlkinud Sara Hännikäinen, Hannu Oittinen ; Ovi / udmurdi keelest soome keelde tõlkinud Kari Sallamaa ; Lumest / udmurdi keelest eesti keelde tõlkinud koostöös autoriga Mihkel Kera ; Ringikujuline lõks ; Nulg ; Maja ; "Maa ühest otsast teise..." ; Vana ajaleht ; Neiu ja karu / udmurdi keelest eesti keelde tõlkinud Irina Orehhova, Kristiina Ehin

  2. Läänemeresoome keelte õppetoolis : kevadseminaril esinejad / Maris Amon

    Index Scriptorium Estoniae

    Amon, Maris

    2000-01-01

    25.-26. veebr. 2000 Tallinna Pedagoogikaülikooli läänemeresoome keelte õppetooli poolt korraldatud Tallinna Pedagoogikaülikooli, Tartu Ülikooli, Joensuu Ülikooli ja Oulu Ülikooli VIRSU-projekti "Emakeele mõju soome ja eesti keele õppimisele ja õpetamisele" kevadseminaril esinesid Heli Laanekask (Oulu Ülikool), Annukka Kataja (TÜ), Leena Nissila (Oulu Ülikool), Jaan Õispuu (TPÜ), Natali Happonen (TÜ), Jüri Valge (TÜ), Annekatrin Kaivapalu (TPÜ), Pirkko Muikku-Werner (Joensuu Ülikool), Helen Sooväli (TPÜ-TÜ), Hannu Remes (Joensuu Ülikool), Ingrid Nikopensius (TÜ)

  3. IBBY Eesti osakond 2007

    Index Scriptorium Estoniae

    2007-01-01

    IBBY Eesti osakond esitas Astrid Lindgreni mälestusauhinna kandidaatideks kirjanik Aino Perviku, illustraatorid Regina Lukk-Toompere ja Ilon Wiklandi. Paabeli Torni auhinna pälvis Arvo Valton komi kirjaniku Vladimir Timini noorsooromaani "Vana-Permi poisi Tikö seiklused" eesti keelde tõlkimise eest. IBBY aunimekirja esitati A. Kivirähk raamatuga "Leiutajateküla Lotte", kunstnik Jüri Mildeberg illustratsioonidega raamatule "Ruttu tuttu" ja tõlkija Piret Saluri Hannu Mäkela raamatu "Härra Huu teeb aiatööd" tõlkimise eest

  4. Are adults with bipolar disorder active? Objectively measured physical activity and sedentary behavior using accelerometry

    OpenAIRE

    Janney, Carol A; Fagiolini, Andrea; Swartz, Holly A.; Jakicic, John M.; Holleman, Robert G.; Richardson, Caroline R

    2013-01-01

    Carol A Janney has received research support from Actigraph, Inc for this study. Andrea Fagiolini is/has been a consultant and/or speaker and/or has received grants from: Angelini, Astra Zeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, Eli Lilly, Janssen, Lundbeck, Novartis, Otsuka, Roche and Sigma Tau. Holly A. Swartz has received honoraria from Servier, Astra Zeneca, SciMed, Bristol-Myers Squibb, Eli Lilly, and Sanofi. She has received royalties from UpToDate. John M. Ja...

  5. 76 FR 16643 - NASA Advisory Council; Aeronautics Committee; Meeting

    Science.gov (United States)

    2011-03-24

    ... requested to comply with Edwards Air Force Base (AFB) and NASA Security. To get to DFRC, you will first need... photo, and a current vehicle registration to gain access to Edwards AFB. While on base, be sure to wear... Flight Research Center (DFRC), Lilly Drive Building 4825, Edwards, CA 93523. Friday, April 15, 2011--The...

  6. Külanäitemäng üllatas tenori ja kooriga / Liisi Seil

    Index Scriptorium Estoniae

    Seil, Liisi, 1971-

    2009-01-01

    17.-19. juulini toimus Lilli külas 4. Nava lava festival. Loeti luulet ja mängiti Jaak Kõdari kirjutatud mulgikeelset näitemängu "Kõik läheb mööda" ning lasteetendust "Hundi ja Rebase lend lõunanabale". Mõlemad lavastas Silvia Soro

  7. Lillikate suvi on Nava Lava päralt / Airi Hallik

    Index Scriptorium Estoniae

    Hallik, Airi, 1975-

    2008-01-01

    Lõuna-Eestis Lilli külas asuva Nava talu Nava Lava suvistest üritustest. Olulisim ettevõtmine oli talu peremehe Jaak Kõdari talu ajaloost kirjutatud näitemängu "Jukra" lavale toomine. Tänavu oli talu aidas avatud ka Lembit Sootsi maalinäitus

  8. Piiriäärne lava valmistub taas esietenduseks / Margus Haav

    Index Scriptorium Estoniae

    Haav, Margus, 1969-

    2008-01-01

    Lõuna-Eestis Lilli külas algaval Nava lava festivalil tuuakse publiku ette Nava talu peremehe Jaak Kõdari näidend "Jukra", lavastaja Silvia Soro. Üht kandvat rolli mängib näitleja Lembit Eelmäe

  9. Rauksi talu lugu rullub Nava Laval / Jaak Kõdar

    Index Scriptorium Estoniae

    Kõdar, Jaak, 1940-

    2010-01-01

    Nava talu peremees Jaak Kõdar talu taastamisest, oma luuleraamatutest ja näidenditest. Lilli külas Nava talus 16.-18. juulini toimuva mulgi kultuuri festivali kava, Nava Laval mängitakse mulgikeelset näitemängu "Rauksi talu lugu"

  10. Grjaznoje proshloje kuklõ Barbi / Igor Silenko

    Index Scriptorium Estoniae

    Silenko, Igor

    2002-01-01

    Nukk Barbie saamislugu - meestele mõeldud seksapiilne saksa nukuke Lilly (autoriks disainer Max Weissbrodt) sai ameerika disaineri Ruth Handleri käe all uue näo ja nime ning debüteeris 1959. a. New Yorgi mänguasjade laadal

  11. A Family Case Study: How Money Might Matter for Academic Learning

    Science.gov (United States)

    Compton-Lilly, Catherine

    2014-01-01

    Many children living in low-income communities do not face struggles in school. Many learn quickly and easily. But for some students, living in a high poverty communities and attending underfunded schools has consequences that can make learning difficult. In this paper, Compton-Lilly draws on the words of a parent living in a low-income community…

  12. 75 FR 8720 - Ocean Transportation Intermediary License Applicants

    Science.gov (United States)

    2010-02-25

    ... 19 of the Shipping Act of 1984 as amended (46 U.S.C. Chapter 409 and 46 CFR 515). Persons knowing of... Individual), Peter Chirichella, President Norton Lilly Logistics, LLC, One St. Louis Centre, Suite 3002.... Holzscheiter, President/CEO (Qualifying Individual), John K. Holzscheiter, Senior Vice President Continental...

  13. 75 FR 1453 - Qualification of Drivers; Exemption Renewals; Vision

    Science.gov (United States)

    2010-01-11

    ... Federal Document Management System (FDMS) at http://www.regulations.gov . Background Under 49 U.S.C. 31136... renewal applications, FMCSA renews the Federal vision exemptions for Linda L. Billings, John A. Chizmar..., Britt D. Hazelwood, William W. Hodgins, Gregory K. Lilly, Michael S. Maki, Larry T. Morrison, Kenneth A...

  14. 76 FR 55467 - Qualification of Drivers; Exemption Applications; Vision

    Science.gov (United States)

    2011-09-07

    ... holidays. SUPPLEMENTARY INFORMATION: Background Under 49 U.S.C. 31136(e) and 31315, FMCSA may renew an.... Buice John A. Chizmar Weldon R. Evans Richard L. Gagnebin Orasio Garcia Leslie W. Good Chester L. Gray James P. Guth Britt D. Hazelwood Gregory K. Lilly Larry T. Morrison Kenneth A. Reddick Leonard Rice, Jr...

  15. Эксклюзивный catwalk в квартале Baltika

    Index Scriptorium Estoniae

    2010-01-01

    9. septembril näidati Baltika kvartalis loomeettevõtlusega tegelejatele välismaalt eesti noorte disainerite eksklusiivset moeetendust "Creative Incubator Fashion Show". Osalejateks Maki, Uma, Donkey Hot, Kalle Aasamäe ja Lilli Jahiloo. Show toimus rahvusvahelise moetegijate kokkutuleku raames, Loomeinkubaatori margi all

  16. The Costs and Benefits of Deferred Giving.

    Science.gov (United States)

    Fink, Norman S.; Metzler, Howard C.

    It is argued in this book that while there can be a significant payoff for deferred giving programs, it is important to determine their cost effectiveness. Modern business methods of cost accounting, benefits analysis, and actuarial and econometric forecasting are applied to the Pomona College plan, whose study was supported by Lilly Endowment,…

  17. 75 FR 34303 - 90th Anniversary of the Department of Labor Women's Bureau, 2010

    Science.gov (United States)

    2010-06-16

    ... Labor Standards Act of 1938, establishing minimum wages and maximum working hours. The Bureau also... as President--the Lilly Ledbetter Fair Pay Restoration Act--builds upon these vital protections to... Proclamation 8533--90th Anniversary of the Department of Labor Women's Bureau, 2010 Proclamation 8534--King...

  18. Pildid räägivad lugusid, vorstid samuti / Andry Ervald

    Index Scriptorium Estoniae

    Ervald, Andry

    2006-01-01

    Koomiksinäitus Rakvere galeriis. Osa võtavad Peeter Krosmann (1971), Kristel Maamägi (1986), Lilli-Krõõt Repnau (1982), Elina Sildre (1980), Joonas Sildre (1980), Veiko Tammjärv (1967), Paco Ulman (1980), Edvin Aedma ja rühmitus Endorfin Fractured Communications. Kristel Maamägi oma töödest

  19. Make love and war ehk ükssarvede ilmumine Tallinnasse = Make love and war, or the unicorns' advent in Tallinn / Rebeka Põldsam

    Index Scriptorium Estoniae

    Põldsam, Rebeka, 1989-

    2012-01-01

    Tallinna linnainstallatsioonide festivali "LIFT11" installatsioonist "Queer-kleepekavihik". Kuraatorid Anna-Stina Treumund ja Jaanus Samma. Autorid Helin Tikerpuu, Katia Weber Piscitelli, Ly Lestberg, Mare Tralla, Ott Pilipenko, Mae Köömnemägi, Andreas Kalkun, Rebeka Põldsam, Lilli-Krõõt Repnau, Aet Kuusik, Jaanus Samma

  20. 75 FR 9333 - Implantation or Injectable Dosage Form New Animal Drugs; Tilmicosin

    Science.gov (United States)

    2010-03-02

    ... supplemental new animal drug application (NADA) filed by Elanco Animal Health, A Division of Eli Lilly & Co. The supplemental NADA provides a dose range for use of an injectable solution of tilmicosin phosphate... to NADA 140-929 for MICOTIL 300 (tilmicosin injection, USP) Injection, available by veterinary...

  1. 75 FR 1275 - New Animal Drugs; Ractopamine

    Science.gov (United States)

    2010-01-11

    ... (NADA) filed by Elanco Animal Health, A Division of Eli Lilly & Co. The supplemental NADA provides for... supplement to NADA 141-221 that provides for use of OPTAFLEXX 45 (ractopamine hydrochloride) Type A medicated... dress. The supplemental NADA is approved as of December 11, 2009, and the regulations in 21 CFR 558.500...

  2. Euroopa Liit hakkab jälgima kodanike telefonikõnesid / Alo Raun

    Index Scriptorium Estoniae

    Raun, Alo, 1981-

    2005-01-01

    EL-i siseministrite otsuse kohaselt on telefoni- ja sidefirmad kohustatud säilitama andmeid kõigi nende võrgu kaudu tehtud kõnede, saadetud lühisõnumite ja e-kirjade kohta, et muutuks lihtsamaks terrorivõrgustike jälgimine. Euroopa Parlamendi liikme Lilli Gruberi kriitikast otsuse kohta. Lisa: Terrorivastased sammud Euroopas

  3. Maalitud majad Zalipies / Marje Tammert

    Index Scriptorium Estoniae

    Tammert, Marje

    2003-01-01

    Poola Zalipie külas on elumajad ja kõrvalhooned dekoreeritud erksavärviliste lillebukettidega. Lilli ja linde näeb aknaluukidel, aiapostidel, kaevudel, käimlatel jm. Küla muuseumis on lilledega kaetud kogu interjöör, kapid, nõud ja tikitud tekstiilid. 4 ill

  4. Performance on Tests of Central Auditory Processing by Individuals Exposed to High-Intensity Blasts

    Science.gov (United States)

    2012-07-01

    this research at the (former) WRAMC. Drs. Frank Musiek and Richard Wilson generously provided essential testing materials. Dr. David Lilly...wnl.0000230197.40410.db 18. Humes LE, Coughlin M, Talley L. Evaluation of the use of a new compact disc for auditory perceptual assessment in the

  5. Grjaznoje proshloje kuklõ Barbi / Igor Silenko

    Index Scriptorium Estoniae

    Silenko, Igor

    2002-01-01

    Nukk Barbie saamislugu - meestele mõeldud seksapiilne saksa nukuke Lilly (autoriks disainer Max Weissbrodt) sai ameerika disaineri Ruth Handleri käe all uue näo ja nime ning debüteeris 1959. a. New Yorgi mänguasjade laadal

  6. The Market, the Military, and a Dynasty: Insurgency Potential in North Korea

    Science.gov (United States)

    2010-03-31

    point between peaceful , if not repressive, coexistence between the regime and the people, and violence? As they did during the colonial years, will...peoples’ grievances against their rulers and made clear that the insurgent must lillie their ideology to the goals of the people. Mao deviated fl:om

  7. Veel üks fond õpetajate toetuseks

    Index Scriptorium Estoniae

    2002-01-01

    Inna Mathiesen annetas sihtasutusele Eesti Rahvuskultuuri Fond oma vanemate mälestuse jäädvustamiseks 300 000 krooni, millega pandi alus Lilly ja Hugo Pärnamäe Fondile. Sellega tahetakse toetada pedagooge, kes on koolis töötanud vähemalt kaks aastat

  8. Erektsioonihäire põhjustest / Anne Veskimeister

    Index Scriptorium Estoniae

    Veskimeister, Anne, 1960-

    2004-01-01

    Androloog Margus Punab, kardioloog Arvo Rosenthal ja psühholoog Imre Rammul tõid möödunud nädalal toimunud ravimifirma Ely Lilly loengupäeval esile erektsioonihäirete põhjused, seosed teiste haigustega ja ravivõimalused

  9. Central Asia: Regional Developments and Implications for U.S. Interests

    Science.gov (United States)

    2009-11-20

    6 Obstacles to Peace and Independence: Regional Tensions and Conflicts...Joanna Lillis , “Kazakhstan: Nazarbayev Dodges President-For-Life Question Ahead of Astana’s OSCE Chairmanship,” Eurasia Insight, November 16, 2009...appeared to be stepping up its aid and trade activities in the region.18 Obstacles to Peace and Independence: Regional Tensions and Conflicts The

  10. Characterization of Emissions and Air Quality Modeling for Predicting the Impacts of Prescribed Burns at DoD Lands

    Science.gov (United States)

    2012-10-01

    States Prescribed Burns with Daysmoke. Atmosphere, 2(3): 358-388. Alessio, G.A., De Lillis , M., Fanelli, M., Pinelli, P. and Loreto, F., 2004. Direct...for Peace and Security Series B-Physics and Biophysics, pp. 189-193. Odman, M.T. and Russell, A.G., 2000. Mass conservative coupling of non

  11. 75 FR 1775 - Notice of Receipt of Requests to Voluntarily Cancel Certain Pesticide Registrations

    Science.gov (United States)

    2010-01-13

    ... change and may be made available on-line at http://www.regulations.gov , including any personal... personal threats. viii. Make sure to submit your comments by the comment period deadline identified. II...-00593 Lilly/Miller Piperonyl butoxide Ready-To-Use Bug- Off Pyrethrins 000829-00200 SA-50 Brand...

  12. The Ripple Effect: Lessons from a Research and Teaching Faculty Learning Community

    Science.gov (United States)

    Hershberger, Andrew; Spence, Maria; Cesarini, Paul; Mara, Andrew; Jorissen, Kathleen Topolka; Albrecht, David; Gordon, Jeffrey J.; Lin, Canchu

    2009-01-01

    Building upon a related 2005 panel presentation at the 25th annual Lilly Conference on College Teaching, Miami University, Oxford, Ohio, the authors, several tenure-track assistant professors and tenured associate professors who have participated in a Research and Teaching Faculty Learning Community at Bowling Green State University, share their…

  13. 30. ja 31. X toimub Kohtla-Järve Linnagaleriis (Tuuslari 18a)...

    Index Scriptorium Estoniae

    2003-01-01

    Avalik seminar ja kunstisündmus "North 2001, West 2002, East 2003", mis võtab kokku rahvusvahelise keskkonnakunsti intensiivkursuse "Be Bounded By..." ja esitleb töötulemusi. Osalevad Limerick Institute of Technology, Eesti Kunstiakadeemia graafikaosakond (Lilli-Krõõt Repnau, Marko Nautras, Tõnis Kenkmaa, Hille Karm, Ly Lestberg), Tampereen Ammattikorkeakoulu, Sheffield Hallam University

  14. Reis kosmosesse : [Floating-kambrist] / Marika Makarova

    Index Scriptorium Estoniae

    Makarova, Marika

    2011-01-01

    Ameerika psühholoogi John C. Lilly poolt kasutusele võetud Floating-kambrist ehk hõljumisvannist, mis aeglustab ajulaineid ning seeläbi aitab vähendada lihaspinget, stressi, ärevust, peavalusid, vererõhku ning parandada und, selgroo- ja kaelavigastusi, suurendada loovust ja heaolu jne

  15. Beyond "It Was Great"? Not so Fast!

    Science.gov (United States)

    Wong, E. David

    2015-01-01

    The Forum on Education Abroad's Ninth Annual Conference in 2013 was organized around the provocative theme, "Moving Beyond It Was Great." In the opening plenary speech, Lilli Engle warned the audience of study abroad researchers, leaders, administrators, and providers that study abroad programs were not as effective as they may want to…

  16. Brain circuits involved in antidepressant response

    OpenAIRE

    Artigas, Francesc

    2010-01-01

    Trabajo presentado al 17 Simposio Científico de Fundación Lilly: From neurobiology to nosology of mental disordes (desde la neurobiología a la nosología de las enfermedades mentales) celebrado en Madrid del 11 al 12 de marso de 2010.-- El pdf es la versión post-print.

  17. Moeloojad võtavad modelliks unarusse jäetud inimesi / Anneli Aasmäe

    Index Scriptorium Estoniae

    Aasmäe, Anneli, 1973-

    2011-01-01

    Eesti Kunstiakadeemia ja Turu Novia ülikooli ühisprojektist "Fashion Empowerment", mille raames kavatsevad tudengid pühenduda mingile spetsiifilise vajadusega inimgrupile sobivate riiete ja jalatsite tegemisele. Projekti juhib moedisainer Lilli Jahilo. Ratastoolikasutajatele hakkab jalatseid disainima nahakunsti eriala tudeng Mari Maripuu

  18. Mõtteid raamatust / Koost. Heigi Aaviste

    Index Scriptorium Estoniae

    1995-01-01

    Aut.: Maire Liivamets, Paul Luhtein, Paul-Eerik Rummo, Maksim Gorki, Johannes Semper, R.Descartes, Valmar Adams, Lilli Promet, Paul Rummo, Cicero, Honoré de Balzac, Aleksandr Pushkin, Epikuros, Debora Vaarandi, Arvi Siig, Helene Johani, Juhan Smuul, Friedebert Tuglas

  19. Värsked värvid amplis ja lillekastis / Kaja Kurg

    Index Scriptorium Estoniae

    Kurg, Kaja, 1959-

    2006-01-01

    Tänavu kasvatatakse lillekastides kõrrelisi ja maitsetaimi, rippuma pannakse suur igihali, suvifloks, shaboonelk jm. Kõige moodsamad õied on viirulised ja träpsulised. Moes on pastelsed ja šokolaadikarva toonid. Uusi ilutaimi ja lilli tutvustab AS Schetelig EV agronoom-müügiesindaja Mall Kaldas. 26 ill

  20. Lugu inimese üksindusest / Õie Orav

    Index Scriptorium Estoniae

    Orav, Õie

    2011-01-01

    Režissöör Veljo Käsperi filmist "Tütarlaps mustas" (1966). Operaator Harry Rehe, stsenarist Lilli Promet. Osades: Gerlinda Kopelman. Juozas Budraitis, Lisl Lindau, Viiu Härm, Jüri Järvet, Evald Hermaküla, Ellen Liiger. Filmi vastuvõtust. Filmi näeb ETV2-s sarjas "Unustatud filmid"

  1. Sügisene moevaatemäng / Britt Rosen

    Index Scriptorium Estoniae

    Rosen, Britt, 1968-

    2008-01-01

    FIBITi moepäevad Viru keskuses, korraldaja Anu Kikas. Arne Niidu, Anu Samarüütel-Longi, Tanel Veenre kollektsioonidest. Kalle Aasamäe, Lilli Jahilo, Aet Alevi, Anu Samarüütel-Longi ja Tanel Veenre kommentaarid

  2. Academic Literacies and Systemic Functional Linguistics: How Do They Relate?

    Science.gov (United States)

    Coffin, Caroline; Donohue, James P.

    2012-01-01

    Two approaches to English for Academic Purposes (EAP) research and teaching which have arisen in recent years are systemic functional linguistics (SFL) approaches in Australia and elsewhere (e.g. Hood, 2006; Lee, 2010; Woodward-Kron, 2009) and Academic Literacies approaches in the UK and elsewhere (e.g. Lillis & Scott, 2008; Thesen &…

  3. Pildid räägivad lugusid, vorstid samuti / Andry Ervald

    Index Scriptorium Estoniae

    Ervald, Andry

    2006-01-01

    Koomiksinäitus Rakvere galeriis. Osa võtavad Peeter Krosmann (1971), Kristel Maamägi (1986), Lilli-Krõõt Repnau (1982), Elina Sildre (1980), Joonas Sildre (1980), Veiko Tammjärv (1967), Paco Ulman (1980), Edvin Aedma ja rühmitus Endorfin Fractured Communications. Kristel Maamägi oma töödest

  4. Drug Advertising and the FDA.

    Science.gov (United States)

    Levesque, Cynthia

    With increases in consumer focused advertising for prescription drugs, the Federal Drug Administration has renewed efforts to protect the public from false advertising. In 1982, it charged that the press kits Eli Lilly and Company distributed to reporters on its new antiarthritis drug, Oraflex, misrepresented the product. It recommended that Lilly…

  5. Harry Potter ja Scarlett käivad kohut / Ilona Martson

    Index Scriptorium Estoniae

    Martson, Ilona, 1970-

    2001-01-01

    Alice Randalli romaan "Tuul on läinud" - samad sündmused kui Margaret Mitchelli romaanis "Tuulest viidud", ainult neegerorjade vaatevinklist. Nancy Stofferi raamatud "Larry Potter ja tema parim sõber Lilly" ja "Legend Rah'ist ja Mugudest" ilmusid 1984. a. Joanne Kathleen Rowlingi "Harry Potter" lood aga valmisid hiljem

  6. Drug Advertising and the FDA.

    Science.gov (United States)

    Levesque, Cynthia

    With increases in consumer focused advertising for prescription drugs, the Federal Drug Administration has renewed efforts to protect the public from false advertising. In 1982, it charged that the press kits Eli Lilly and Company distributed to reporters on its new antiarthritis drug, Oraflex, misrepresented the product. It recommended that Lilly…

  7. Drapeeringuid ja volte mitut moodi / Tanel Veenre

    Index Scriptorium Estoniae

    Veenre, Tanel, 1977-

    2011-01-01

    Hanna Korsari uue moekollektsiooni esitlusest 11. märtsil Tartus Tasku keskuses. Liina Steini, Kalle Aasamäe, Xenia Joosti ja Lilli Jahilo uute moekollektsioonide esitlusest 11. märtsil Tallinnas Viru keskuses. Ivo Nikkolo kaubamärgi uue kollektsiooni esitlusest Tallinnas Harju mäe liuväljal

  8. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder

    DEFF Research Database (Denmark)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn;

    2014-01-01

    for major depressive disorder. DATA SOURCES: Clinical study reports, including protocols as appendices (total 13,729 pages), were obtained from the EMA in May 2011. Journal articles were identified through relevant literature databases and contacting the manufacturer, Eli Lilly. Clinicaltrials...

  9. The Costs and Benefits of Deferred Giving.

    Science.gov (United States)

    Fink, Norman S.; Metzler, Howard C.

    It is argued in this book that while there can be a significant payoff for deferred giving programs, it is important to determine their cost effectiveness. Modern business methods of cost accounting, benefits analysis, and actuarial and econometric forecasting are applied to the Pomona College plan, whose study was supported by Lilly Endowment,…

  10. [Comparision of forced expiratory time, recorded by two spirometers with flow sensors of various types, and acoustic duration of tracheal forced expiratory noises].

    Science.gov (United States)

    Malaeva, V V; Pochekutova, I A; Korenbaum, V I

    2015-01-01

    In the sample of 44 volunteers forced expiratory time values obtained in spirometers, equipped with flow sensor of Lilly type and turbine flow sensor, and acoustic duration of tracheal forced expiratory noises are compared. It is shown that spirometric forced expiratory time is dependent on flow sensor type. Therefore it can't be used in diagnostic aims.

  11. Lummavaid ja ahistavaid stseene raudse eesriide tagant / Marianne Kõrver

    Index Scriptorium Estoniae

    Kõrver, Marianne, 1980-

    2008-01-01

    1968. aastal Eesti Telefilmis valminud 3-osaline mängufilm "Pimedad aknad" Lilli Prometi jutustuse "Pimedate akende aegu" järgi : režissöör Tõnis Kask : operaator Anton Mutt : helilooja Eino Tamberg : osades Ada Lundver, Marianne Leover, Jaak Tamleht, Ao Peep. Filmi mõju kriitikule 40 aastat hiljem restaureeritud varianti vaadates

  12. Moeloojad võtavad modelliks unarusse jäetud inimesi / Anneli Aasmäe

    Index Scriptorium Estoniae

    Aasmäe, Anneli, 1973-

    2011-01-01

    Eesti Kunstiakadeemia ja Turu Novia ülikooli ühisprojektist "Fashion Empowerment", mille raames kavatsevad tudengid pühenduda mingile spetsiifilise vajadusega inimgrupile sobivate riiete ja jalatsite tegemisele. Projekti juhib moedisainer Lilli Jahilo. Ratastoolikasutajatele hakkab jalatseid disainima nahakunsti eriala tudeng Mari Maripuu

  13. Gordon Conference on Microbial Adhesion

    Science.gov (United States)

    1988-07-01

    Sweden Al fa-Laval, Sweden Eli Lilly Monsanto Barnes-Hind Labs Bristol -Myers Pfizer Gillette Following the conference, many positive comments were...clays and metals: R. Mitchell, discussion leader -’S- F. Dazzo, Attachment of Rhizobium trifolii to 9:00-9:45 a.m. white clover root hairs. E. Bayer

  14. Neljakümnes kevad : [luuletused] / Niina Obrezkova ; tlk. Arvo Valton

    Index Scriptorium Estoniae

    Obrezkova, Niina, 1965-

    2006-01-01

    Sisu: Neljakümnes kevad ; "Oleme kõik lapsed..." ; "Hommikvestlust pidada on hilja..." ; "Kingi mulle lilli sa..." ; "On mehi..." ; "Mälu mulle uksed avas ise..." ; "Kolm on valu südames..." ; "Helge pisar..." ; "Ei salahoovusi mus leidu..." "Miskitviisi...". Luuletused paralleelselt komi ja eesti keeles

  15. Clinical utility of orally disintegrating olanzapine in Chinese patients with schizophrenia: a review of effectiveness, patient preference, adherence, and other properties

    Directory of Open Access Journals (Sweden)

    Zhao J

    2014-02-01

    Full Text Available Jingping Zhao,1 Jianjun Ou,1 Haibo Xue,2 Li Liu,2 William Montgomery,3 Tamas Treuer4 1Mental Health Institute of The Second Xiangya Hospital, Hunan Province Technology Institute of Psychiatry, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, Hunan, 2Lilly Suzhou Pharmaceutical Co, Ltd, Jiangsu, People's Republic of China; 3Global Health Outcomes, Eli Lilly and Company, Sydney, Australia; 4Emerging Markets Business Unit (Neuroscience, Eli Lilly and Company, Budapest, Hungary Abstract: The primary objective of this systematic review was to examine the evidence for the efficacy, effectiveness, and safety of orally disintegrating olanzapine in Chinese populations. A systematic literature search was conducted using databases covering international and Chinese journals, ClinicalTrials.gov, and internal and external trial registries at Eli Lilly and Company using search terms related to target countries (People's Republic of China, Hong Kong, and Taiwan and orally disintegrating olanzapine treatment. A publication and one clinical study report were retrieved. The clinical study showed orally disintegrating olanzapine and the standard oral tablet to have similar efficacy and tolerability profiles. A bioequivalence study has shown that orally disintegrating olanzapine and the standard oral tablet have similar pharmacokinetic profiles. Orally disintegrating olanzapine and the standard oral tablet have similar efficacy and tolerability profiles. Keywords: orally disintegrating, olanzapine, Chinese, schizophrenia, patients

  16. Neljakümnes kevad : [luuletused] / Niina Obrezkova ; tlk. Arvo Valton

    Index Scriptorium Estoniae

    Obrezkova, Niina, 1965-

    2006-01-01

    Sisu: Neljakümnes kevad ; "Oleme kõik lapsed..." ; "Hommikvestlust pidada on hilja..." ; "Kingi mulle lilli sa..." ; "On mehi..." ; "Mälu mulle uksed avas ise..." ; "Kolm on valu südames..." ; "Helge pisar..." ; "Ei salahoovusi mus leidu..." "Miskitviisi...". Luuletused paralleelselt komi ja eesti keeles

  17. Reis kosmosesse : [Floating-kambrist] / Marika Makarova

    Index Scriptorium Estoniae

    Makarova, Marika

    2011-01-01

    Ameerika psühholoogi John C. Lilly poolt kasutusele võetud Floating-kambrist ehk hõljumisvannist, mis aeglustab ajulaineid ning seeläbi aitab vähendada lihaspinget, stressi, ärevust, peavalusid, vererõhku ning parandada und, selgroo- ja kaelavigastusi, suurendada loovust ja heaolu jne

  18. 77 FR 4228 - New Animal Drugs for Use in Animal Feeds; Monensin

    Science.gov (United States)

    2012-01-27

    ... drug application (NADA) filed by Elanco Animal Health, A Division of Eli Lilly & Co. The supplemental NADA provides for approval of free-choice feeds for growing cattle on pasture or in dry lot (stocker... Corporate Center, Indianapolis, IN 46285, filed a supplement to NADA 95-735 that provides for use...

  19. 76 FR 79064 - New Animal Drugs for Use in Animal Feeds; Monensin

    Science.gov (United States)

    2011-12-21

    ... drug application (NADA) filed by Elanco Animal Health, A Division of Eli Lilly & Co. The supplemental NADA revises a manufacturing specification for monensin free-choice Type C medicated feed for growing... 46285, filed a supplement to NADA 95-735 that provides for use of RUMENSIN 90 (monensin, USP) Type...

  20. Harry Potter ja Scarlett käivad kohut / Ilona Martson

    Index Scriptorium Estoniae

    Martson, Ilona, 1970-

    2001-01-01

    Alice Randalli romaan "Tuul on läinud" - samad sündmused kui Margaret Mitchelli romaanis "Tuulest viidud", ainult neegerorjade vaatevinklist. Nancy Stofferi raamatud "Larry Potter ja tema parim sõber Lilly" ja "Legend Rah'ist ja Mugudest" ilmusid 1984. a. Joanne Kathleen Rowlingi "Harry Potter" lood aga valmisid hiljem

  1. Эксклюзивный catwalk в квартале Baltika

    Index Scriptorium Estoniae

    2010-01-01

    9. septembril näidati Baltika kvartalis loomeettevõtlusega tegelejatele välismaalt eesti noorte disainerite eksklusiivset moeetendust "Creative Incubator Fashion Show". Osalejateks Maki, Uma, Donkey Hot, Kalle Aasamäe ja Lilli Jahiloo. Show toimus rahvusvahelise moetegijate kokkutuleku raames, Loomeinkubaatori margi all

  2. Make love and war ehk ükssarvede ilmumine Tallinnasse = Make love and war, or the unicorns' advent in Tallinn / Rebeka Põldsam

    Index Scriptorium Estoniae

    Põldsam, Rebeka, 1989-

    2012-01-01

    Tallinna linnainstallatsioonide festivali "LIFT11" installatsioonist "Queer-kleepekavihik". Kuraatorid Anna-Stina Treumund ja Jaanus Samma. Autorid Helin Tikerpuu, Katia Weber Piscitelli, Ly Lestberg, Mare Tralla, Ott Pilipenko, Mae Köömnemägi, Andreas Kalkun, Rebeka Põldsam, Lilli-Krõõt Repnau, Aet Kuusik, Jaanus Samma

  3. Networked Success and Failure at Hybritech

    Science.gov (United States)

    Jones, Mark Peter

    2011-01-01

    The author presents an historical account of scientific work conducted at a commercial biotech firm in San Diego called Hybritech. It tells of disruptions in research programs following the acquisition of the company by the pharmaceutical giant Eli Lilly in 1986. The story centers on responses to an organizational challenge that research managers…

  4. Recognition of Prior Learning--Normative Assessment or Co-Construction of Preferred Identities?

    Science.gov (United States)

    Hamer, Jen

    2010-01-01

    Recognition of prior learning (RPL) has been an important element of Australia's Vocational Education and Training (VET) policy since it was officially adopted as a key national principle in 1991 (VEETAC 1991, cited in Wilson and Lilly 1996:2). The aim of RPL is to formally assess a person's skills gained through life and work experience, in order…

  5. Factors affecting treatment adherence to atomoxetine in ADHD: a systematic review

    Directory of Open Access Journals (Sweden)

    Treuer T

    2016-05-01

    Full Text Available Tamás Treuer,1 Luis Méndez,2 William Montgomery,3 Shenghu Wu4 1Neuroscience Research, Eli Lilly and Company, Budapest, Hungary; 2Eli Lilly de Mexico, Mexico City, Mexico; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 4Neuroscience Research, Eli Lilly Asia, Inc, Shanghai, People’s Republic of China Abstract: The purpose of this paper was to systematically review the literature related to research about the factors affecting treatment adherence and discontinuation of atomoxetine in pediatric, adolescent, and adult patients with attention-deficit/hyperactivity disorder (ADHD. Medline was systematically searched using the following prespecified terms: “ADHD”, “Adherence”, “Compliance”, “Discontinuation”, and “Atomoxetine”. We identified 31 articles that met all inclusion and exclusion criteria. The findings from this review indicate that persistence and adherence to atomoxetine treatment were generally high. Factors found to influence adherence and nonadherence to atomoxetine treatment in ADHD in this review include age, sex, the definition of response used, length of treatment, initial dose of treatment, comorbid conditions, and reimbursement. Tolerability was cited as an important reason for treatment discontinuation. More research is needed to understand those factors that can help to identify patients at risk for poor adherence and interventions that could improve treatment adherence early in the stage of this illness to secure a better long-term prognosis. Keywords: atomoxetine, treatment discontinuation, adherence, compliance, ADHD medication, relapse

  6. Robert Aymar receives one of the highest Finnish distinctions

    CERN Multimedia

    2008-01-01

    On 9 December 2008 Robert Aymar, CERN Director-General, was awarded the decoration of Commander, first class, of the Order of the Lion of Finland by the President of the Republic of Finland. This decoration, one of the highest of Finland, was presented in a ceremony by the Ambassador Hannu Himanen, Permanent Representative of Finland to the UN and other international organisations in Geneva. Robert Aymar was honoured for his service to CERN, the LHC, his role in the cooperation between Finland and CERN, as well as his contribution to science in general. In his speech the ambassador underlined CERN’s efforts in the field of education, mentioning the High school teachers programme.

  7. Clinical development of galunisertib (LY2157299 monohydrate, a small molecule inhibitor of transforming growth factor-beta signaling pathway

    Directory of Open Access Journals (Sweden)

    Herbertz S

    2015-08-01

    Full Text Available Stephan Herbertz,1 J Scott Sawyer,2 Anja J Stauber,2 Ivelina Gueorguieva,3 Kyla E Driscoll,4 Shawn T Estrem,2 Ann L Cleverly,3 Durisala Desaiah,2 Susan C Guba,2 Karim A Benhadji,2 Christopher A Slapak,2 Michael M Lahn21Lilly Deutschland GmbH, Bad Homburg, Germany; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK; 4Lilly Research Laboratories, Eli Lilly and Company, New York, NY, USA Abstract: Transforming growth factor-beta (TGF-β signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. Furthermore, galunisertib has antitumor activity in tumor-bearing animal models such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous long-term exposure to galunisertib caused cardiac toxicities in animals requiring adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow further development. The use of such a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib. These efforts resulted in an intermittent dosing regimen (14 days on/14 days off, on a 28-day cycle of galunisertib for all ongoing trials. Galunisertib is being investigated either as monotherapy or in combination with standard antitumor regimens (including nivolumab

  8. Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

    Directory of Open Access Journals (Sweden)

    Anand E

    2016-10-01

    Full Text Available Ernie Anand,1 Lovisa Berggren,2 John Landry,3 Ágoston Tóth,4 Holland C Detke5 1Neuroscience Medical Affairs, Eli Lilly & Company Ltd, Windlesham, UK; 2Global Statistical Sciences, Lilly Deutschland GmbH, Bad Homburg, Germany; 3Global Statistical Sciences, Eli Lilly Canada Inc., Toronto, ON, Canada; 4Neuroscience, Lilly Hungary, Budapest, Hungary; 5Psychiatry and Pain Disorders, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Background: The objective of the present analysis is to determine the impact of the 3-hour observation period for olanzapine long-acting injection (LAI on patient satisfaction and well-being by comparing data collected before and after its implementation. Methods: This is a post hoc analysis of patients treated with olanzapine LAI in 1 a 6-month fixed-dose randomized controlled trial and/or 2 a 6-year open-label safety study. This analysis was limited to patients with schizophrenia who were treated with olanzapine LAI consistent with the approved indication and dosing recommendations of the European Union Summary of Product Characteristics (N=966. Of the 966 patients, the analysis further focused only on those patients who received both 1 at least one injection before the implementation of the 3-hour observation period and 2 at least one injection after implementation of the 3-hour observation period (N=487. Patient satisfaction was assessed with the three-item Patient Satisfaction with Medication Questionnaire-Modified. Responses were averaged across all postbaseline visits occurring before (ie, without the implementation of the 3-hour observation period and across all postbaseline visits occurring after (ie, with the implementation of the 3-hour observation period. In addition, the rate of postinjection delirium/sedation syndrome events was calculated. Results: There was no meaningful change after implementation of the 3-hour observation period in satisfaction (before: mean [SD] =4.0 [1.02] and

  9. Large-eddy simulation of the diurnal cycle of the atmospheric boundary layer and influence of the radiative forcing during the Wangara experiment.

    Science.gov (United States)

    Dall'Ozzo, Cédric; Carissimo, Bertrand; Milliez, Maya; Musson-Genon, Luc; Dupont, Eric

    2013-04-01

    The ability to simulate the whole diurnal cycle of the atmospheric boundary layer in order to study the complex turbulent structures remains a difficult topic. Consequently large-eddy simulations (LES) are performed with the open source CFD code Code_Saturne [Archambeau et al., 2004]. First the code is validated on an atmospheric convective case [Schmidt and Schumann, 1989] where different subgrid-scale (SGS) models are compared: two non-dynamical SGS models [Smagorinsky, 1963] [Nicoud and Ducros, 1999] and two dynamical SGS models [Germano et al., 1991 ; Lilly, 1992] [Wong and Lilly, 1994]. Then LES are performed to simulate the whole diurnal cycle of the Wangara experiment (Day 33-34). The results are compared to measurements , RANS "k-ɛ" model and other LES performed by [Basu et al., 2008] using a locally averaged scale-dependent dynamic (LASDD) SGS model. Thereafter the influence of the radiative forcing on the atmosphere is studied testing several SGS models. The results are especially discussed on nocturnal low level jet and potential temperature gradient in the stable boundary layer. References: [Archambeau et al., 2004] Archambeau F., Mehitoua N., Sakiz M. (2004). Code_Saturne: a finite volume code for the computation of turbulent incompressible flows. International Journal on Finite Volumes 1(1). [Basu et al., 2008] Basu S., Vinuesa J. F., and Swift A. (2008). Dynamic LES modeling of a diurnal cycle. Journal of Applied Meteorology and Climatology, 47 :1156-1174. [Germano et al., 1991] Germano M., Piomelli U., Moin P., and Cabot W. H. (1991). A dynamic subgrid-scale eddy-viscosity model. Physics of Fluids, A3 :1760-1765. [Lilly, 1992] Lilly D. K. (1992). A proposed modification of the Germano subgrid-scale closure method. Physics of Fluids, A 4 :633-635. [Schmidt and Schumann, 1989] Schmidt H. and Schumann U. (1989). Coherent structure of the convective boundary layer derived from lage-eddy simulation. Journal of Fluid Mechanics, 200 :511-562. [Smagorinsky

  10. Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder

    DEFF Research Database (Denmark)

    Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn

    2014-01-01

    OBJECTIVE: To determine, using research on duloxetine for major depressive disorder as an example, if there are inconsistencies between protocols, clinical study reports, and main publicly available sources (journal articles and trial registries), and within clinical study reports themselves...... for major depressive disorder. DATA SOURCES: Clinical study reports, including protocols as appendices (total 13,729 pages), were obtained from the EMA in May 2011. Journal articles were identified through relevant literature databases and contacting the manufacturer, Eli Lilly. Clinicaltrials...... to discontinuation but with no apparent bias. In each trial, a median of 406 (range 177-645) and 166 (100-241) treatment emergent adverse events (adverse events that emerged or worsened after study drug was started) in the randomised phase were not reported in journal articles and Lilly trial registry reports...

  11. Empowering the community to manage diabetes better: An integrated partnership-based model

    Directory of Open Access Journals (Sweden)

    Arun Bamne

    2016-01-01

    Full Text Available Context : Rising number of diabetes cases in India calls for collaboration between the public and private sectors. Aims: Municipal Corporation of Greater Mumbai (MCGM partnered with Eli Lilly and Company (India [Eli Lilly] to strengthen the capacity of their diabetes clinics. Materials and Methods : Medical Officers, dispensaries and Assistant Medical Officers (AMOs located at attached health posts were trained on an educational tool, Diabetes Conversation Map™ (DCM by a Master Trainer. This tool was then used to educate patients and caregivers visiting the MCGM diabetes clinics. Results : Twenty-eight centers conducted 168 sessions, and 1616 beneficiaries availed the education over six months. General feedback from health providers was that DCM helps clear misconceptions among patients and caregivers in an interactive way and also improves compliance of patients. Conclusions : This communication highlights a unique public-private partnership where the sincere efforts of public sector organization (MCGM were complemented by the educational expertise lent by a private firm.

  12. FDA approval of comparative claims for prescription drugs--the Moxam case.

    Science.gov (United States)

    Marcus, D

    1983-01-01

    FDA allowance of comparative claims as part of the approved labeling for new prescription drugs creates special problems. Claims contained in prescription drug labeling are viewed by physicians as embodying not just the normal puffery of the manufacturer, but the considered views of government agency charged with protecting public health. Thus, labeling claims for prescription drugs have an impact and significance that promotional claims for other products do not. In the Moxam case--a dispute between Upjohn and Lilly over the FDA's approval of a comparative claim for a new Lilly antibiotic--the agency recognized this fundamental reality. Faced with the prospect of having to provide a procedure to permit competitors to challenge approval of comparative claims, the FDA has moved toward a policy of not permitting such claims in labeling, while allowing them in advertising.

  13. Sleep disturbance in mental health problems and neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    Anderson KN

    2013-05-01

    Full Text Available Kirstie N Anderson1 Andrew J Bradley2,3 1Department of Neurology, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne, UK; 2Eli Lilly and Company Limited, Lilly House, Basingstoke, UK; 3Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK Abstract: Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed. Keywords: sleep, mental health, neurodegenerative disorders, cognition

  14. Changing Mindsets to Transform Security: Leader Development for an Unpredictable and Complex World

    Science.gov (United States)

    2013-01-01

    years, especially in areas of chronic disease. Diabetes was untreatable for many prior to mid-1983 when human insulin became available for the...security educators, and leverages the combined potential of digital technology and the technical literacy of the next generation of learners...Lilly in 1982 and made its way to the mar- ket shortly thereafter. Irl B. Hirsch and Jay S. Skyler, “The Management of Type 1 Diabetes ,” in Diabetes

  15. Report on the International Rarefied Gas Dynamics Symposium (29th) held in Xi’an, China on 13-18 July 2014

    Science.gov (United States)

    2014-11-21

    logistics and timing proceeded very smoothly. The layout of the coffee –break venues were nicely suited to interactions between the participants. The printed...program had some very useful features: A page showing the whole week with a color scheme distinguishing session types. A program summary with a page...see the details in the list of reactions that was shown to sort out why. Jacob Graul and Taylor Lilly were the authors of "Coherent Rayleigh

  16. Impact of Insurance Status on Health Care Utilization and Quality of Self-Care Among Ethnic Minorities with Type 2 Diabetes

    Science.gov (United States)

    2004-01-01

    year randomized control study to examine the effects of diet and lifestyle modifications or medication (i.e., metformin ) on the incidence of Type 2...R. (1998). The effects of treatment on the direct costs of diabetes. Diabetes Care, 21 (3S), 19C-24C. Hsia, J., Kemper, E., Sofaer, S., Bowen, D...Caucasians (Trevino, 1999) and cost was more of a barrier than race in their minds (Lillie-Blanton et al., 2000). Thus, the issue of socioeconomic

  17. GENEVIEW and the DNACE data bus: computational tools for analysis, display and exchange of genetic information.

    OpenAIRE

    1986-01-01

    We describe an interactive computational tool, GENEVIEW, that allows the scientist to retrieve, analyze, display and exchange genetic information. The scientist may request a display of information from a GenBank locus, request that a restriction map be computed, stored and superimposed on GenBank information, and interactively view this information. GENEVIEW provides an interface between the GenBank data base and the programs of the Lilly DNA Computing Environment (DNACE). This interface sto...

  18. Irregular Warfare: A Selected Bibliography

    Science.gov (United States)

    2009-11-01

    Effectiveness: Peace Operations and Beyond. Clementsport: Cana- dian Peacekeeping Press, 2007. 92pp. (JZ5538 .M21 2007) 24 Muse, Robert C...100.2/ADA482274 Lilly , Douglas D. Strategic Framing of Stability Operations. Strategy Research Project. Carlisle Barracks: U.S. Army War College, 20...able in Informaworld 28 OTHER BIBLIOGRAPHIES Armstrong, Glenda, comp. Peace and Stability Operations. Maxwell Air Force Base: Muir S. Fair

  19. DSCA: General Population Evacuation of Texas and Louisiana

    Science.gov (United States)

    2010-06-01

    USNORTHCOM produced a planning guide titled, “General Population Evacuation by Air.” Rear Admiral 8 Lilli , who served as the director of the...standalone entity is not possible when military assets are employed in any other worldwide operation. However, in times of peace it may be possible to...and recent history, periods of “ peace ” will not exist for quite some time. For the purposes of this study it is assumed that the 26 military

  20. Striking the Right Balance: Fusion Centers and Privacy

    Science.gov (United States)

    2010-09-01

    for example. In 2007, Lillie Coney delivered a statement on behalf of the organization to the Department of Homeland Security’s Data Privacy and...use of fusion centers to collect information concerning peace activists and political dissenters (German & Stanley, 2008). According to the ACLU...update report, the Maryland State Police monitored the activities of a well-known peace activist and shared his identifying information with a number of

  1. Impacts of U.S. Export Control Policies on Science and Technology Activities and Competitiveness

    Science.gov (United States)

    2009-02-25

    international cooperation with foreign nations and/or consortia on space activities that are of mutual benefit and that further the peaceful ...mutual benefit and that further the peaceful exploration and use of space, as well as to advance national security, homeland security, and foreign...Technology, Cambridge, MA Gail H. Cassell, Vice President, Scientific Affairs and Distinguised Lilly Research Scholar for Infectious Diseases, Eli

  2. Inimeste teadlikkus arendab ravimiturgu / Rauno Pukonen ; ref. Enn Tosso

    Index Scriptorium Estoniae

    Pukonen, Rauno

    2003-01-01

    Ilmunud ka: Delovõje Vedomosti 15. okt. lk. 14. Eli Lilly juhatuse esimehe Rauno Pukoneni ettekandest Äripäeva konverentsil Äriplaan 2004. Ettekandja sõnul on Eesti ravimiturg ebaatraktiivne ja ettearvamatu, kompenseeritavate ravimite valik on kesine, Eesti tarbija jääb väga paljudest ravimitest ilma. Kommenteerib AS-i Magnum Medical juhatuse liige Tarmo Laanetu. Vt. samas: Ravimiturg riigi lõa otsas. Diagramm

  3. Public Citizen敦促ED药应有可能的视力丧失“黑框警告”

    Institute of Scientific and Technical Information of China (English)

    金伟秋(摘)

    2006-01-01

    美国消费者团体Public Citizen向美国FDA提出请求,要求在Pfizer公司的Viagra(sildenadil,西地那而)(Ⅰ)及两种其它勃起功能障碍(ED)药Lilly Icos公司的Cialis(tadalafil)及Levitra(vardenafil)的标签上加入有可能导致不可逆的视力丧失的黑框警告。

  4. Anidulafungin: ECB, LY 303366, V-echinocandin, VEC, VER 002, VER-02.

    Science.gov (United States)

    2003-01-01

    Vicuron Pharmaceuticals (formerly Versicor Inc.) is developing anidulafungin [LY 303366, ECB, V-echinocandin, VEC, VER-02, VER 002], a lipopeptide echinocandin B derivative, for IV treatment of mycoses. Anidulafungin acts against fungal infection by inhibiting beta-1,3-glucan synthase, an enzyme essential for cell wall formation. Anidulafungin was originally developed for oral use by Eli Lilly and was undergoing phase II clinical trials in the UK and the US for the treatment of Candida, Aspergillus and Pneumocystis carinii infections. However, Eli Lilly discontinued development of the oral formulation due to poor oral bioavailability. In May 1999, Versicor obtained exclusive worldwide commercialisation rights to anidulafungin with responsibility for its development and clinical registration. Under the terms of the agreement, Eli Lilly received a signing fee, and will receive milestone payments upon future development of anidulafungin and royalties on future sales. Eli Lilly also retains an option for the development of an oral formulation of the compound. On 3 March 2003, Versicor Inc. of Fremont (California, USA) and Biosearch Italia SpA of Milan (Italy) announced the completion of a merger agreement, whereby Biosearch was merged with and into Versicor in a stock-for-stock exchange valued at US dollars 260.7 million. The combined company temporarily kept the name Versicor until the new name, Vicuron Pharmaceuticals, was announced on 26 March 2003. In January 2003, Versicor announced that positive results from a phase II trial for anidulafungin IV treatment involving 120 patients in the US with invasive candidiasis/candidaemia, have led to another double-blind, randomised phase III trial being conducted in the US, Canada and Europe for this indication. This additional phase III trial will enrol approximately 300 patients to investigate the efficacy of IV anidulafungin (200 mg loading dose followed by 100 mg maintenance dose) versus IV fluconazole for 10 to 42 days

  5. Fundamentals of neurobiology.

    Science.gov (United States)

    Greg Hall, D

    2011-01-01

    Session 1 of the 2010 STP/IFSTP Joint Symposium on Toxicologic Neuropathology, titled "Fundamentals of Neurobiology," was organized to provide a foundation for subsequent sessions by presenting essential elements of neuroanatomy and nervous system function. A brief introduction to the session titled "Introduction to Correlative Neurobiology" was provided by Dr. Greg Hall (Eli Lilly and Company, Indianapolis, IN). Correlative neurobiology refers to considerations of the relationships between the highly organized and compartmentalized structure of nervous tissues and the functioning within this system.

  6. Bioaccumulation and Effects on Reproduction in Aquatic Organisms: An Assessment of the Current Literature

    Science.gov (United States)

    1985-09-01

    Macdonald, W. R. Lillie, and A. Lutz. 1983. Joint toxicity of mercury and selenium in salmonid eggs. Arch. Environ. Contam. Toxicol. 12:415-419. Lagler, K...Neanthes arenaceodentata (Poly- chaeta). Mar. Environ. Res. 5:41-49. Ozoh, P. T. E. and C.-O. Jacobson. 1979. Embryotoxicity and hatchability in...Jr. 1983. Chronic effects of selenite- selenium on Daphnia pulex. Arch. Environ. Contam. Toxicol. 12:399-404. Richter, J. E., S. F. Peterson, and C. F

  7. As Mobile Goes, So Goes the Corps: A Look At Change Inside A Government Agency

    Science.gov (United States)

    2006-01-01

    had been successfully competing with foreign firms for years. IBM, Eli Lilly and Company, Coca - Cola , 3M, and Eastman-Kodak are good examples...water projects, and entrenched defiance to change. One interviewee recalled that the Corps has been likened to an 蟰- pound gorilla." However...economic methodology used by the Corps of Engineers to calculate the return on investment in a given project. CPAR-Construction Productivity Advancement

  8. The Auditory System of the Minke Whale (Balaenoptera Acutorostrata): A Potential Fatty Sound Reception Pathway in a Mysticete Cetacean

    Science.gov (United States)

    2012-09-01

    remains unclear (Lillie, 1910; Fraser and Purves , 1960). This elongated glove finger is not found in odontocetes or any other mammals. Another...times past and present, and to its external and internal characteristics. Ray Society Publication. Fraser FC, Purves PE. 1960. Anatomy and...presumed to exist in the peribullar sinus while the animal is diving (Fraser and Purves , 1960). The simulation results show that these air spaces

  9. 流行情报

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    去奉献爱心吧 Kristine Lilly Predator限量版球鞋;时尚族群的最爱;全是为了健康着想 Motopure H12蓝牙耳机;享受户外的新鲜空气 Bates Footwear登山鞋;好音乐大家听 Zune2外接音箱……

  10. Glucagon Kits: Are Your Patients Prepared for a Hypoglycemic Emergency

    Science.gov (United States)

    2016-06-03

    study. If this is a technical publication/presentation, state the type (e .g. case report. QA/QI study. program evaluation study, informational report...for home reference. Glucagon training kits were obtained from both Lilly and Novo Nordisk for training in the clinic. We share a free phone app ...felt to increase the confidence needed during an emergency. Many of our patients stated that there were only children in the home and most

  11. Letter to the Editor - responses to Weisntein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-I-like mitogenic and antiactivity in cultured cancer cells.

    Science.gov (United States)

    Weinstein, Doron; Simon, Meital; Yehezkel, Einat; Laron, Zvi; Werner, Haim

    2013-08-20

    We thank the team of Eli Lilly and Company for their critical appraisal of our study and for giving us the opportunity to clarify a number of points [1]. We agree with Kazda et al. that randomized clinical trials will best address any direct relationship between insulin analogues and cancer in man. We do not question the fact that tight control of blood glucose has dramatically advanced the lives of patients with diabetes. This article is protected by copyright. All rights reserved.

  12. Applying Knowledge Management Theory to Army Doctrine Development: Case Study of a Web-Based Community of Practice

    Science.gov (United States)

    2007-12-14

    Clark, Ph.D. , Member COL Timothy R. Reese , M.A. , Member Steven M. Carmichael, M.A. Accepted this 14th day of December...the doctrine development process. I cannot give enough thanks to my committee, Dr. Tom Clark, COL Tim Reese , and Mr. Steven Carmichael who spent many...35Ibid., 27. 36Ibid., 36. 37Ibid. 38Anne Chapman, Benjamin King, and Carol Lilly, Transforming the Army, TRADOC’s First Thirty Years, 1973-2003

  13. Inactivation of Bacillus Anthracis Spores Using Carbon Nanotubes

    Science.gov (United States)

    2014-10-30

    the attachment of B. anthracis spores, when in combination with natural peptide nisin, it can inhibit the biofilm formation from B. anthrancis spores...McCoy, Chang Yang, Wei Chen, Ebenezer Addae, Liju Yang. Investigation of Gold/ Copper Sulfide Core/Shell Nanoparticles’ Antimicrobial Activity to...1. “Effect of Gold/ Copper Sulfide Core/Shell Nanoparticles on Bacillus Anthracis Spores and Cells”, E. Addae1, M. Lilly1, E. McCoy1, C. Yang2, W

  14. The Ncar East in the 21st Century

    Directory of Open Access Journals (Sweden)

    Wigand Ritter

    2012-10-01

    Full Text Available Although an "avalanche of people" may be expected in thenear future lillie confidence seems to be justified with respect toa peaceful and prosperous development in the Near East. Politicalantagonism, often fuelled by religious intolerance threatei!Sor even pre1·ents the evaluation of promising opportunities atthis huge area between the Old World continents which couldotlwwise benefit so much from the by-passing great world trafficroutes.

  15. Ensaios terapêuticos com penicilina: III - Bouba (Framboesia, pian, yaws: (continuação: penicilina de procedência americana, empregada em doses baixas também cura aparentemente esta enfermidade

    Directory of Open Access Journals (Sweden)

    A. M. da Cunha

    1944-10-01

    Full Text Available Five patients of yaws were treated with american Penicillin (Squibb, Winthrop and Lilly, in small dosis. The treatment has been performed, using 200 Oxford units each 4 hours. The total amount of units "per" subject, has varied from 24.000 to 54.000. A complete disappearence of the external lesions was obtained between the 12th and the 25th day of treatment.

  16. Bauhäusler on the Franco-Spanish Border

    OpenAIRE

    Laura Martínez de Guereñu

    2016-01-01

    This article focuses on the travels of Bauhaus masters and instructors and on the transport of Bauhaus products to Spain in 1929, when the Franco-Spanish border was still culturally permeable. Ludwig Mies van der Rohe and Marcel Breuer introduced their tubular-steel furniture in the Spanish market. Mies and Lilly Reich designed the interiors of all German industrial sections at the Barcelona International Exposition, where the Bauhaus sent objects from its carpentry, metal, and weaving worksh...

  17. Predictors of antipsychotic monotherapy with olanzapine during a 1-year naturalistic study of schizophrenia patients in Japan

    Directory of Open Access Journals (Sweden)

    Ye W

    2012-01-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Jennifer A Flynn3, Yuka Tanji3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People's Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Although expert guidelines for the treatment of schizophrenia recommend antipsychotic monotherapy, the use of antipsychotic polypharmacy is common. This study identified characteristics that differentiate patients with schizophrenia who are treated with olanzapine monotherapy versus polypharmacy in usual care in Japan.Patients and methods: In a large (N = 1850 prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Consistent with past research, antipsychotic polypharmacy was defined as the concurrent use of olanzapine and another antipsychotic for at least 60 days. Switching was defined as discontinuing a prior antipsychotic therapy rather than augmenting the medication regimen. Predictors of antipsychotic monotherapy were based on information available at the time of olanzapine initiation. Baseline characteristics were compared using t-tests and Χ2 tests. Stepwise logistic regression was used to identify independent predictors of monotherapy.Results: Patients treated with olanzapine monotherapy (43.2% differed from those treated with antipsychotic polypharmacy (56.8% on demographics, treatment history, baseline symptom levels, functional levels, and treatment-emergent adverse events. Stepwise logistic regression identified multiple variables that significantly predicted monotherapy: older age, shorter duration of schizophrenia, outpatient status, comorbid medical conditions, lower body mass index, no prior anticholinergic use, no prior mood stabilizer use, and switching from a previous antipsychotic (typical or atypical

  18. Associations between adherence and outcomes among older, type 2 diabetes patients: evidence from a Medicare Supplemental database

    Directory of Open Access Journals (Sweden)

    Boye KS

    2016-08-01

    Full Text Available Kristina Secnik Boye,1 Sarah E Curtis,1 Maureen J Lage,2 Luis-Emilio Garcia-Perez3 1Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 2HealthMetrics Outcomes Research, LLC, Bonita Springs, FL, 3Global Medical Affairs, Lilly Diabetes, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA Objective: To examine the association between adherence to glucose-lowering agents and patient outcomes, including costs, acute-care resource utilization, and complications, in an older, type 2 diabetic population.Data and methods: The study used Truven’s Medicare Supplemental database from July 1, 2009 to June 30, 2014. Patients aged 65 years or older were included if they had at least two type 2 diabetes diagnoses and received a glucose-lowering agent from July 1, 2010 through June 30, 2011. Multivariable analyses examined the relationships among 3-year patient outcomes and levels of adherence, proxied by the proportion of days covered. Outcomes included all-cause medical costs, diabetes-related medical costs, acute-care resource utilization, and acute complications.Results: In this study (N=123,235, higher adherence was linked to reduced costs and improved health outcomes. For example, comparing an individual with adherence of proportion of days covered <20% to one with proportion of days covered ≥80% illustrates an average saving of $28,824 in total 3-year costs. Furthermore, a 1% increase in adherence among 1,000 patients was associated with all-cause savings of $65,464 over 3 years. The probability of a hospitalization, an emergency room (ER visit, or an acute complication decreased monotonically as adherence levels got higher, as did the number of hospitalizations, ER visits, and days hospitalized (P<0.005.Conclusion: Higher adherence was associated with substantially less need for acute care, as indicated by a lowered probability of hospitalization or ER use, a reduced

  19. Timbermash-Baikal成为John Deere的林业设备在西伯利亚(Siberia)的新经销商

    Institute of Scientific and Technical Information of China (English)

    秦莉

    2006-01-01

    John Deere公司与西伯利亚的Timbermash—Baikal签署了新的经销合同,新的经销商Timbermash—Baikal要负责西伯利亚地区John Deere生产的新旧设备的销售、使用培训和销后服务工作。Timbermash—Baikal位于伊尔库茨克(Irkutsk),但是它的销售和服务业务却包括布拉茨克(Bratsk)和克拉斯诺亚尔斯克(Krasnojarsk)地区。John Deere公司的总经理HannuHietikko说:“西伯利亚是俄国林业发展很快的地方,而中国也需要很多木质原材料,西伯利亚有2亿m3的木材可砍伐,但目前只有4000万m3被开发利用了,而且其中90%都需要将整棵树砍倒,John Deere公司拥有伐木及加工原木的设备,

  20. Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Wacheck V

    2011-05-01

    Full Text Available Volker Wacheck1, Michael Lahn2, Gemma Dickinson3, Wolfgang Füreder4, Renata Meyer4, Susanne Herndlhofer4, Thorsten Füreder1, Georg Dorfner5, Sada Pillay2, Valérie André6, Timothy P Burkholder7, Jacqueline K Akunda8, Leann Flye-Blakemore9, Dirk Van Bockstaele9, Richard F Schlenk10, Wolfgang R Sperr4, Peter Valent4,111Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 2Early Oncology Clinical Investigation, Eli Lilly and Company, Indianapolis, IN, USA; 3Department of Pharmacokinetics, Eli Lilly and Company, Erl Wood Research Centre, Windlesham, Surrey, UK; 4Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria; 5Eli Lilly GesmbH, Medical Department, Vienna, Austria; 6Department of Statistics, Eli Lilly and Company, Erl Wood Research Centre, Surrey, UK; 7Discovery Chemistry Research and Technology, Eli Lilly and Company, Indianapolis, IN, USA; 8Nonclinical Toxicology, Eli Lilly and Company, Indianapolis, IN, USA; 9Flow Cytometry and Cell Analysis, Esoterix Clinical Trials Services, Mechelen, Belgium; 10Universitätsklinikum Ulm, Klinik für Innere Medizin III, Ulm, Germany; 11Ludwig Boltzmann Cluster Oncology, Vienna, AustriaBackground: Acute myeloid leukemia (AML is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug–drug interactions (DDI were assessed.Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg

  1. Impact of anxiety symptoms on outcomes of depression: an observational study in Asian patients

    Directory of Open Access Journals (Sweden)

    Novick D

    2016-04-01

    Full Text Available Diego Novick,1 William Montgomery,2 Jaume Aguado,3 Xiaomei Peng,4 Josep Maria Haro3 1Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Parc Sanitari Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 4Eli Lilly and Company, Indianapolis, IN, USA Objective: To investigate the impact of anxiety symptoms on depression outcomes in Asian patients with major depressive disorder (MDD (n=714. Methods: The 17-item Hamilton Depression Scale (HAMD-17, overall severity, somatic symptoms, and quality of life (QOL (EuroQOL Questionnaire-5 Dimensions [EQ-5D] were assessed at baseline and 3 months. Anxiety was measured using items 10 and 11 from the HAMD-17. Linear, tobit, and logistic multiple regression models analyzed the impact of anxiety symptoms on outcomes. Baseline anxiety was related to age and the presence of pain symptoms at baseline. Results: Regression models showed that a higher level of anxiety was associated with a lower frequency of remission and lower QOL at 3 months. Patients with lower baseline anxiety symptoms had higher remission rates (odds ratio for each point of anxiety symptoms, 0.829 [95% confidence interval [CI]: 0.723–0.951]. Patients with higher levels of baseline anxiety had a lower QOL at 3 months (a decrease in EQ-5D tariff score for each point of anxiety symptoms, 0.023 [95% CI: 0.045–0.001]. Conclusion: In conclusion, the presence of anxiety symptoms negatively impacts the outcomes of depression. Keywords: depression, anxiety, Asia, observational, outcomes

  2. Comparison of patients undergoing switching versus augmentation of antipsychotic medications during treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2012-03-01

    Full Text Available Haya Ascher-Svanum, Alan JM Brnabic, Anthony H Lawson, Bruce J Kinon, Virginia L Stauffer, Peter D Feldman, Katarina KelinLilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USAAbstract: It is often difficult to determine whether a patient may best benefit by augmenting their current medication or switching them to another. This post-hoc analysis compares patients’ clinical and functional profiles at the time their antipsychotic medications were either switched or augmented. Adult outpatients receiving oral antipsychotic treatment for schizophrenia were assessed during a 12-month international observational study. Clinical and functional measures were assessed at the time of first treatment switch/augmentation (0–14 days prior and compared between Switched and Augmented patient groups. Due to low numbers of patients providing such data, interpretations are based on effect sizes. Data at the time of change were available for 87 patients: 53 Switched and 34 Augmented. Inadequate response was the primary reason for treatment change in both groups, whereas lack of adherence was more prevalent in the Switched group (26.4% vs 8.8%. Changes in clinical severity from study initiation to medication change were similar, as indicated by Clinical Global Impressions–Severity scores. However, physical and mental component scores of the 12-item Short-Form Health Survey improved in the Augmented group, but worsened in the Switched group. These findings suggest that the patient’s worsening or lack of meaningful improvement prompts clinicians to switch antipsychotic medications, whereas when patients show some improvement, clinicians may be more likely to try bolstering the improvements through augmentation. Current findings are consistent with physicians’ stated reasons for switching versus augmenting antipsychotics in the treatment of schizophrenia. Confirmation of these findings requires further research

  3. Predictors of continuation with olanzapine during the 1-year naturalistic treatment of patients with schizophrenia in Japan

    Directory of Open Access Journals (Sweden)

    Ye W

    2011-12-01

    Full Text Available Wenyu Ye1, Haya Ascher-Svanum2, Yuka Tanji3, Jennifer A Flynn3, Michihiro Takahashi3,41Lilly Suzhou Pharmaceutical Co, Shanghai, People’s Republic of China; 2Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories Japan, Eli Lilly Japan KK, Kobe, 4Terauchi-Takahashi Psychiatric Clinic, Ashiya, JapanPurpose: Treatment continuation is considered an important measure of antipsychotic effectiveness in schizophrenia, reflecting the medication’s efficacy, safety, and tolerability from both patients’ and clinicians’ perspectives. This study identified characteristics of patients with schizophrenia who continue olanzapine therapy for a 1-year period in Japan.Methods: In a large (N = 1850, prospective, observational study, Japanese patients with schizophrenia who initiated treatment with olanzapine were followed for 1 year. Baseline characteristics were compared using t-tests and chi-square tests. Stepwise logistic regression was used to identify independent baseline predictors of treatment continuation.Results: Most patients (68.2% continued with olanzapine therapy for the full 1-year study period, with an average duration of 265.5 ± 119.4 days. At baseline, patients who continued were significantly more likely to be male, older, and inpatients; have longer illness duration, higher negative and cognitive symptoms, better health-related quality of life, and prior anticholinergic use. Continuers were significantly less likely to engage in social activities, live independently, work for pay, or have prior antidepressant use. Continuers showed significantly greater early (3-month improvement in global symptom severity. Logistic regression found that continuation was significantly predicted by longer illness duration, lower positive symptoms, higher negative symptoms, and better health-related quality of life.Conclusions: In this large naturalistic study in Japan, most patients with schizophrenia stayed on olanzapine therapy for

  4. Nava tiigi ääres seiklevad Hunt ja Rebane / Liisi Seil ; kommenteerinud Pille Põllumäe

    Index Scriptorium Estoniae

    Seil, Liisi, 1971-

    2009-01-01

    17.-19. juulini Lilli külas Nava talus toimuvast 4. Nava lava festivalist. 19. 07 mängib Karksi valla kultuurikeskuse noorteteater "O" lasteetendust "Hundi ja Rebase lend lõunanabale", mille on Nava talu peremehe Jaak Kõdari raamatu "Kriimureinulised lood. 3, Argonaudid" põhjal kirjutanud ja lavastanud Silvia Soro. Kostüümid tegi Thea Ilusmets. 17., 18. ja 19. 07 mängitakse Jaak Kõdari mulgikeelset külanäitemängu "Kõik läheb mööda, kõik tuleb jälle. 1912-1918", lavastaja Silvia Soro

  5. Küsitlus : Kas olete rahul, et Toomas Hendrik Ilves saab presidendiks?

    Index Scriptorium Estoniae

    2006-01-01

    Küsimusele vastavad Karksi valla Lilli küla vanem, Aasta Ema 2005 Alli Laande, kirikuõpetaja Eenok Haamer, olümpiavõitja Andrus Veerpalu, laulja Uno Loop, Aasta Isa 2000 Ants Taul, poetess Ave Alavainu, Talupidajate Keskliidu esimees Arvo Veidenberg, Külmsoo talu peremees Põlvamaalt Raivo Musting, Laatre Piima juhataja Edda Vahtramäe, Virumaa teraviljakasvataja Jaak Läänemets, maalikunstnik Navitrolla ja koorijuht Ants Üleoja. Ilmunud ka: Meie Kodu 4. okt. 2006, lk. 2

  6. Do concomitant pain symptoms in patients with major depression affect quality of life even when taking into account baseline depression severity?

    Directory of Open Access Journals (Sweden)

    Novick D

    2013-05-01

    Full Text Available Diego Novick,1 William Montgomery,2 Zbigniew Kadziola,3 Victoria Moneta,4 Xiaomei Peng,5 Roberto Brugnoli,6 Josep Maria Haro41Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Eli Lilly Austria GmbH, Vienna, Austria; 4Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 5Eli Lilly and Company, Indianapolis, IN, USA; 6Università di Roma, “Sapienza,” Rome, ItalyBackground: Patients with major depressive disorder (MDD may suffer from concomitant pain symptoms. The aim of this study is to determine whether the presence of painful physical symptoms (PPS influences quality of life when taking into account baseline depression severity.Methods: Patients with a new or first episode of MDD (n = 909 were enrolled in a 3-month prospective observational study in East Asia. The Hamilton Depression Rating Scale, Clinical Global Impression-Severity score, Somatic Symptom Inventory, and EuroQoL questionnaire-5 Dimensions (EQ-5D and EQ-Visual Analogue Scale (EQ-VAS were assessed at baseline and 3 months’ follow-up. The presence of PPS was defined as a mean score of ≥2 on the Somatic Symptom Inventory pain-related items. Regression analyses determined predictors of quality of life at 3 months, adjusting for age, sex, depressive symptoms, overall severity, and quality of life at baseline.Results: PPS were present (PPS+ at baseline in 52% of patients. During the 3-month follow-up, EQ-VAS scores improved from 47.7 (standard deviation [SD] 20.6 to 72.5 (SD 20.4, and EQ-5D improved from 0.48 (SD 0.34 to 0.80 (SD 0.26. At 3 months, mean EQ-VAS was 66.4 (SD 21.2 for baseline PPS+ patients versus 78.5 (SD 17.6 for baseline PPS- patients, and mean EQ-5D was 0.71 (SD 0.29 versus 0.89 (SD 0.18. PPS+ at baseline was a significant predictor of quality of life at 3 months after adjusting for sociodemographic and baseline clinical variables

  7. The personal, societal, and economic burden of schizophrenia in the People's Republic of China: implications for antipsychotic therapy

    Directory of Open Access Journals (Sweden)

    Montgomery W

    2013-08-01

    Full Text Available William Montgomery,1 Li Liu,2 Michael D Stensland,5 Hai Bo Xue,2 Tamas Treuer,4 Haya Ascher-Svanum31Eli Lilly and Company, Sydney, NSW, Australia; 2Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People's Republic of China; 3Eli Lilly and Company, Global Health Outcomes, Indianapolis, IN, USA; 4Eli Lilly and Company, Budapest, Hungary; 5Agile Outcomes Research, Inc, Rochester, MN, USABackground: This article describes the personal, societal, and economic burden attributable to schizophrenia in the People's Republic of China and highlights the potential for effective outpatient treatment to reduce this burden given recent changes in the Chinese health care system. The importance of effective antipsychotic therapy in reducing the burden of schizophrenia is also examined.Methods: Published research on the burden, disability, management, and economic costs of schizophrenia in the People's Republic of China was examined in the context of the larger body of global research. Research written in English or Chinese and published before June 2012 was identified using PubMed, CNKI, and Wanfang Med database searches. The contribution of effective antipsychotic therapy in reducing the risk for relapse and hospitalization and improving patients' functioning is described.Results: Schizophrenia imposes a substantial burden on Chinese society, with indirect costs accounting for the majority of the total cost. Functional impairment is high, leading to lost wages and work impairment. In the People's Republic of China, schizophrenia is the most common diagnosis among hospitalized psychiatric patients. Ongoing changes in the Chinese health care system may reduce some barriers to effective relapse prevention in schizophrenia and potentially reduce hospitalizations. The use of antipsychotics for acute episodes and maintenance treatment has been shown to decrease symptom severity and reduce the risk for relapse and hospitalization. However, discontinuing

  8. The Effort of Building Faculty Learning Communities in America%美国高校教师学习共同体的构建——对话美国迈阿密大学教学促进中心主任米尔顿·克斯教授

    Institute of Scientific and Technical Information of China (English)

    詹泽慧; 李晓华

    2009-01-01

    @@ 编者按:米尔顿.D.克斯(Milton D.Cox)是迈阿密大学教学促进中心(center for the Enhancement of Learning and Teaclling,CELT,它是美国四大模范教学促进中心之一.)的主任和学术期刊和的主编.他创建并负责主持一年一度的国际性高校教学盛会--百合论坛(Lilly Conference).

  9. Systematic review of raloxifene in postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia

    Directory of Open Access Journals (Sweden)

    Fujiwara S

    2014-11-01

    Full Text Available Saeko Fujiwara,1 Etsuro Hamaya,2 Masayo Sato,2 Peita Graham-Clarke,3 Jennifer A Flynn,2 Russel Burge41Hiroshima Atomic Bomb Casualty Council, Hiroshima, Japan; 2Lilly Research Laboratories Japan, Eli Lilly Japan K.K., Kobe, Japan; 3Global Health Outcomes, Eli Lilly Australia, Sydney, NSW, Australia; 4Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USAPurpose: To systematically review the literature describing the efficacy, effectiveness, and safety of raloxifene for postmenopausal Japanese women with osteoporosis or low bone mass (osteopenia.Materials and methods: Medline via PubMed and Embase was systematically searched using prespecified terms. Retrieved publications were screened and included if they described randomized controlled trials or observational studies of postmenopausal Japanese women with osteoporosis or osteopenia treated with raloxifene and reported one or more outcome measures (change in bone mineral density [BMD]; fracture incidence; change in bone-turnover markers, hip structural geometry, or blood–lipid profile; occurrence of adverse events; and change in quality of life or pain. Excluded publications were case studies, editorials, letters to the editor, narrative reviews, or publications from non-peer-reviewed journals; multidrug, multicountry, or multidisease studies with no drug-, country-, or disease-level analysis; or studies of participants on dialysis.Results: Of the 292 publications retrieved, 15 publications (seven randomized controlled trials, eight observational studies were included for review. Overall findings were statistically significant increases in BMD of the lumbar spine (nine publications, but not the hip region (eight publications, a low incidence of vertebral fracture (three publications, decreases in markers of bone turnover (eleven publications, improved hip structural geometry (two publications, improved blood–lipid profiles (five publications, a low incidence of hot flushes

  10. Internet-Based Education for Prostrate Cancer Screening. Addendum

    Science.gov (United States)

    2010-12-01

    that addressed the benefits of screening (e.g., “I am worried about PCa and screening may give me peace of mind”) and five items that addressed the...Broadband Adoption. 2008[ http://pewresearch.org/pubs/888/home-broadband- adoption-2008]. 69. Lillie SE, Brewer NT, O’Neill SC, Morrill EF, Dees EC...worried about PCa and screening may give me peace of mind”), and half of which addressed the limitations of screening (e.g., “I do not want to risk

  11. Laps(epõlv) 19. sajandi teise poole Eestis omaelulooliste tekstide näitel. Child(hood) in 19th Century Estonia: a Study of Autobiographical Texts

    OpenAIRE

    Ave Mattheus

    2012-01-01

    In this article I discuss autobiographical texts which focus on children and childhood in late 19th century Estonia. Childhood memories as well as other autobiographical material became popular in Estonia in the 1920s-1930s, when most of the studied works--the memoirs by Anna Haava, Mait Metsanurk, Jaan Lattik, Jaan Vahtra, Friedebert Tuglas, August Kitzberg and Marta Sillaots--were written. Some texts come from the 19th century (e.g. Lilli Suburg’s autobiographical works) or early 20th centu...

  12. The current status of immunotoxins: an overview of experimental and clinical studies as presented at the Third International Symposium on Immunotoxins.

    Science.gov (United States)

    Uckun, F M; Frankel, A

    1993-02-01

    The Third International Symposium on Immunotoxins was held on June 19-21, 1992 in Orlando, Florida. This symposium was sponsored by NATO, NIH, Pierce Chemical Company, Walt Disney Cancer Institute at Florida Hospital, Duke Comprehensive Cancer Center, Xoma, Immunogen, Seragen, Bristol-Myers Squibb, Chiron, Ortho Biotech, Upjohn, Merck Sharp & Dohme Research Laboratories, Abbot Laboratories, Lilly Research Laboratories, and Evans & Sutherland. The Pierce Immunotoxin Award which recognizes outstanding contributions to immunotoxin research and development, was presented to Drs David FitzGerald, Fatih Uckun, David Eisenberg, and Ira Wool, for their contributions to the immunotoxin field.

  13. Nava tiigi ääres seiklevad Hunt ja Rebane / Liisi Seil ; kommenteerinud Pille Põllumäe

    Index Scriptorium Estoniae

    Seil, Liisi, 1971-

    2009-01-01

    17.-19. juulini Lilli külas Nava talus toimuvast 4. Nava lava festivalist. 19. 07 mängib Karksi valla kultuurikeskuse noorteteater "O" lasteetendust "Hundi ja Rebase lend lõunanabale", mille on Nava talu peremehe Jaak Kõdari raamatu "Kriimureinulised lood. 3, Argonaudid" põhjal kirjutanud ja lavastanud Silvia Soro. Kostüümid tegi Thea Ilusmets. 17., 18. ja 19. 07 mängitakse Jaak Kõdari mulgikeelset külanäitemängu "Kõik läheb mööda, kõik tuleb jälle. 1912-1918", lavastaja Silvia Soro

  14. GETDB: 104326 [GETDB

    Lifescience Database Archive (English)

    Full Text Available 104326 Link to Original w[*]; P{GawB}NP2790 / CyO 23B7 Link to DGRC Genome Viewer: 10432... Genetics. CyO Link to clone table - 1 1014 Link to cluster table 1014 1 Request - sg sg sg internal lethal - - - - - - Show 10432...6 DGRC Number 104326 Link to Original Genotype w[*]; P{GawB...}NP2790 / CyO Insertion Site 23B7 Map Viewer Link to DGRC Genome Viewer: 104326 Related Genes NTPase lilli O

  15. MES的应用与发展

    Institute of Scientific and Technical Information of China (English)

    张志檩

    2006-01-01

    @@ 国外流程工业的MES MES属于企业管理应用软件的范围,起源于离散工业,又扩展到流程工业.据统计,在企业管理应用软件中,除ERP产品和厂商外,MES产品及其厂商中,Invensys、SIEMENS、Emerson Process Management、 ASPEN Tech、 Indus International、 Honeywell Hispec Solutions、 Rockwell Software、 ABB、 Kronos Inc. GE Fanuc Automation、 Agile Software Corp.、 OSI Software、SimSci、 Wonderware、 HITACHI、 YOKOGAWA、 Technomatix Tech、Lilly Software等公司都名列前茅.

  16. Complete NACA Muroc Staff of 1947, in front of the XS-1 and B-29

    Science.gov (United States)

    1947-01-01

    The NACA Muroc Contingent in October 1947 in front of the Bell Aircraft Corporation X-1-2 and Boeing B-29 launch aircraft. Standing left to right: Le Roy Proctor, Jr., Don Borchers, Harold Nemecek, Phyllis Actis Rogers, Milton McLaughlin, Roxanah Yancey, Arthur 'Bill' Vernon, Dorothy Clift Hughes, Naomi C. Wimmer, Frank Hughes, John Mayer, Elmer Bigg, De E. Beeler. Kneeling left to right: Charles Hamilton, Joseph Vensel, Herbert Hoover, Hubert Drake, Eugene Beckwith, Walter Williams, Harold Goodman, Howard Lilly, John Gardner.

  17. The Effects of High Velocity Variable Mass Projectiles on the Maxillofacial Complex,

    Science.gov (United States)

    1980-06-01

    high number of severe maxillofacial injuries ; the trench protected the body, the helmet protected the head, and the face was the major point of exposure...information concerning combat casualty management of maxillofacial injuries becomes even more significant when the following quotes from Emergency War...Tinder, L.E., Osbon, D.B., Lilly, G.E., Salem, J.E., and Cutcher, J.L.: Maxillofacial Injuries Sustained in the Vietnam Conflict Mil Med. 134:668, 1969. 151 i" •

  18. Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen; Rasmussen, Mette H; Christensen, Mikkel

    2010-01-01

    Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog being developed by Eli Lilly for the treatment of type 2 diabetes mellitus (T2DM). Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from...... effects on HbA1c and body weight. If dulaglutide possesses similar efficacy to other GLP-1 analogs, the once-weekly treatment will most likely be welcomed by patients with T2DM....

  19. The Makassar Strait Pycnocline Variability at 20-40 Days

    Science.gov (United States)

    2012-04-25

    2008GL036372. Kundu . P.K.. Cohen. I.M.. 2004. Fluid Mechanises. Elsevier. New York. Lilly. J.M.. Rhines. P.B.. 2002. Coherent Eddies in the Labrador Sea...tends to speed up the neighboring fluid particles after it has reached the Mak-East site, and causes a more negative (southward) i/. Conversely, the...column extending from the surface to 1000 m isobath. To investigate the generating mechanism of eddies at the Labani Channel, we analyze the output of

  20. Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Eby EL

    2015-06-01

    Full Text Available Elizabeth L Eby,1 Kate Van Brunt,2 Cynthia Brusko,3 Bradley Curtis,4 Maureen J Lage5 1Global Patient Outcomes and Real World Evidence, Eli Lilly and Co., Indianapolis IN USA; 2Eli Lilly and Co., Windlesham, UK; 3Lilly USA, LLC, Indianapolis, IN, USA; 4Eli Lilly and Co., Indianapolis, IN, USA; 5HealthMetrics Outcomes Research, LLC, Bonita Springs, FL, USA Objective: To examine costs, resource utilization, adherence, and hypoglycemic events among various doses of U-100 insulin regimens among elderly patients (age ≥65 years diagnosed with diabetes.Methods: Truven Health Analytics Medicare databases from January 1, 2008 through December 31, 2011 were utilized. General linear models with a gamma distribution and log link were used to examine costs, while logistic and negative binomial regressions were used to examine resource utilization and hypoglycemic events. Analyses controlled for patient characteristics, pre-period comorbidities, general health, and use of antidiabetic medications as well as index dose of insulin.Results: All-cause inpatient, emergency room, and outpatients costs, as well as diabetes-related inpatient costs, were highest among individuals who were treated with an index dose of 10–100 units/day followed by >300 units/day, while drug costs and total costs generally increased as index dosage increased. Resource utilization generally followed the same pattern as costs, with number of office visits increasing as the dose increased and the highest hospital length of stay, number of hospitalizations, number of emergency room visits, and number of diabetes-related hospitalizations were generally highest among those in the lowest and highest index dose cohorts. Compared to patients who initiated with an index dose of 10–100 units/day, all other patients were significantly less likely to achieve an adherence threshold of 80% based upon index dose range, and while those with an index dose of >100–150 units/day were

  1. Predictors of premature discontinuation of treatment in multiple disease states

    Directory of Open Access Journals (Sweden)

    Eric Nantz

    2009-01-01

    Full Text Available Eric Nantz1, Hong Liu-Seifert2, Vladimir Skljarevski21Department of Statistics, Western Michigan University, Kalamazoo, MI, USA; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USABackground: Premature discontinuation of treatment impacts outcomes of clinical practice. The traditional perception has been patient discontinuation is mainly driven by unwanted side effects. Systematic analysis of data from clinical trials across several disease states was performed to identify predictors of premature discontinuation during clinical interventions.Methods: A post hoc analysis was conducted on 22 randomized, double-blind, placebo-controlled clinical trials for treatment of fibromyalgia, diabetic peripheral neuropathic pain, major depressive disorder, and generalized anxiety disorder. Analyses were conducted on pooled data within each disease state.Results: Lack of early therapeutic response was a significant predictor of patient discontinuation in each disease state. Visit-wise changes in therapeutic response and severity of adverse events were also significant risk factors, with change in therapeutic response having a higher significance level in three disease states. Patients who discontinued due to adverse events had similar therapeutic responses as patients completing treatment.Conclusion: Contrary to the conventional belief that premature treatment discontinuation is primarily related to adverse events, our findings suggest lack of therapeutic response also plays a significant role in patient attrition. This research highlights the importance of systematic monitoring of therapeutic response in clinical practice as a measure to prevent patients’ discontinuation from pharmacological treatments.Keywords: attrition, depression, generalized anxiety disorder, fibromyalgia, therapeutic response, adverse event

  2. Open innovation for phenotypic drug discovery: The PD2 assay panel.

    Science.gov (United States)

    Lee, Jonathan A; Chu, Shaoyou; Willard, Francis S; Cox, Karen L; Sells Galvin, Rachelle J; Peery, Robert B; Oliver, Sarah E; Oler, Jennifer; Meredith, Tamika D; Heidler, Steven A; Gough, Wendy H; Husain, Saba; Palkowitz, Alan D; Moxham, Christopher M

    2011-07-01

    Phenotypic lead generation strategies seek to identify compounds that modulate complex, physiologically relevant systems, an approach that is complementary to traditional, target-directed strategies. Unlike gene-specific assays, phenotypic assays interrogate multiple molecular targets and signaling pathways in a target "agnostic" fashion, which may reveal novel functions for well-studied proteins and discover new pathways of therapeutic value. Significantly, existing compound libraries may not have sufficient chemical diversity to fully leverage a phenotypic strategy. To address this issue, Eli Lilly and Company launched the Phenotypic Drug Discovery Initiative (PD(2)), a model of open innovation whereby external research groups can submit compounds for testing in a panel of Lilly phenotypic assays. This communication describes the statistical validation, operations, and initial screening results from the first PD(2) assay panel. Analysis of PD(2) submissions indicates that chemical diversity from open source collaborations complements internal sources. Screening results for the first 4691 compounds submitted to PD(2) have confirmed hit rates from 1.6% to 10%, with the majority of active compounds exhibiting acceptable potency and selectivity. Phenotypic lead generation strategies, in conjunction with novel chemical diversity obtained via open-source initiatives such as PD(2), may provide a means to identify compounds that modulate biology by novel mechanisms and expand the innovation potential of drug discovery.

  3. Facts and fictions about polymorphism.

    Science.gov (United States)

    Cruz-Cabeza, Aurora J; Reutzel-Edens, Susan M; Bernstein, Joel

    2015-12-01

    We present new facts about polymorphism based on (i) crystallographic data from the Cambridge Structural Database (CSD, a database built over 50 years of community effort), (ii) 229 solid form screens conducted at Hoffmann-La Roche and Eli Lilly and Company over the course of 8+ and 15+ years respectively and (iii) a dataset of 446 polymorphic crystals with energies and properties computed with modern DFT-d methods. We found that molecular flexibility or size has no correlation with the ability of a compound to be polymorphic. Chiral molecules, however, were found to be less prone to polymorphism than their achiral counterparts and compounds able to hydrogen bond exhibit only a slightly higher propensity to polymorphism than those which do not. Whilst the energy difference between polymorphs is usually less than 1 kcal mol(-1), conformational polymorphs are capable of differing by larger values (up to 2.5 kcal mol(-1) in our dataset). As overall statistics, we found that one in three compounds in the CSD are polymorphic whilst at least one in two compounds from the Roche and Lilly set display polymorphism with a higher estimate of up to three in four when compounds are screened intensively. Whilst the statistics provide some guidance of expectations, each compound constitutes a new challenge and prediction and realization of targeted polymorphism still remains a holy grail of materials sciences.

  4. Tadalafil once daily in the management of erectile dysfunction: patient and partner perspectives

    Directory of Open Access Journals (Sweden)

    Pierre Costa

    2009-04-01

    Full Text Available Pierre Costa1, Thierry Grivel2, Naji Gehchan31Service d’Urologie–Andrologie, Hôpital Caremeau, Nîmes, France; 2159, Avenue Sainte-Marguerite, Nice, France; 3Eli Lilly and Company, Lilly France – Medical Division, Suresnes, FranceAbstract: Erectile dysfunction (ED is a prevalent condition that affects men and their partners. Significant improvements in the sexual lives of these couples have been achieved with the introduction of phosphodiesterase 5 (PDE5 inhibitors. A PDE5 inhibitor is now widely recognized as the first-line therapy for the majority of men with ED. Currently, three PDE5 inhibitors – sildenafil, tadalafil and vardenafil – are approved to be taken as needed in anticipation of sexual activity, but only one of these, tadalafil, has been approved to be taken once daily. The primary aims of this review are to summarize the patients’ and partners’ viewpoints of ED management with PDE5 inhibitors, and to determine whether once-daily tadalafil can contribute to improving some psychological aspects of ED (such as sexual self-confidence, spontaneity and time concerns compared with on-demand tadalafil or other PDE5 inhibitors taken by patients with ED.Keywords: erectile dysfunction, once-daily treatment, patient and partner perspectives, phosphodiesterase 5 (PDE5 inhibitor

  5. Drotrecogin alfa (activated)...a sad final fizzle to a roller-coaster party.

    Science.gov (United States)

    Angus, Derek C

    2012-02-06

    Following the failure of PROWESS-SHOCK to demonstrate efficacy, Eli Lilly and Company withdrew drotrecogin alfa (activated) from the worldwide market. Drotrecogin was initially approved after the original trial, PROWESS, was stopped early for overwhelming efficacy. These events prompt consideration of both the initial approval decision and the later decision to withdraw. It is regrettable that the initial decision was made largely on a single trial that was stopped early. However, the decision to approve was within the bounds of normal regulatory practice and was made by many approval bodies around the world. Furthermore, the overall withdrawal rate of approved drugs remains very low. The decision to withdraw was a voluntary decision by Eli Lilly and Company and likely reflected key business considerations. Drotrecogin does have important biologic effects, and it is probable that we do not know how best to select patients who would benefit. Overall, there may still be a small advantage to drotrecogin alfa, even used non-selectively, but the costs of determining such an effect with adequate certainty are likely prohibitive, and the point is now moot. In the future, we should consider ways to make clinical trials easier and quicker so that more information can be available in a timely manner when considering regulatory approval. At the same time, more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response.

  6. The riddle of sex: biological theories of sexual difference in the early twentieth-century.

    Science.gov (United States)

    Ha, Nathan Q

    2011-01-01

    At the turn of the twentieth century, biologists such as Oscar Riddle, Thomas Hunt Morgan, Frank Lillie, and Richard Goldschmidt all puzzled over the question of sexual difference, the distinction between male and female. They all offered competing explanations for the biological cause of this difference, and engaged in a fierce debate over the primacy of their respective theories. Riddle propounded a metabolic theory of sex dating from the late-nineteenth century suggesting that metabolism lay at the heart of sexual difference. Thomas Hunt Morgan insisted on the priority of chromosomes, Frank Lillie emphasized the importance of hormones, while Richard Goldschmidt supported a mixed model involving both chromosomes and hormones. In this paper, I will illustrate how the older metabolic theory of sex was displaced when those who argued for the relatively newer theories of chromosomes and hormones gradually formed an alliance that accommodated each other and excluded the metabolic theory of sex. By doing so, proponents of chromosomes and hormones established their authority over the question of sexual difference as they laid the foundations for the new disciplines of genetics and endocrinology. Their debate raised urgent questions about what constituted sexual difference, and how scientists envisioned the plasticity and controllability of this difference. These theories also had immediate political and cultural consequences at the turn of the twentieth century, especially for the eugenic and feminist movements, both of which were heavily invested in knowledge of sex and its determination, ascertainment, and command.

  7. The promotion of olanzapine in primary care: an examination of internal industry documents.

    Science.gov (United States)

    Spielmans, Glen I

    2009-07-01

    Media reports have discussed how olanzapine was marketed off-label for dementia and subsyndromal bipolar disorder. Much of this marketing occurred in primary care settings. However, these reports have provided few details. In legal proceedings, Lilly disclosed internal documents that detail the strategies utilized to market olanzapine. The current paper addresses the marketing of olanzapine in detail based upon a review of these documents. All 358 documents released by Lilly are publicly available online. Documents were utilized for this review if they were relevant to the marketing of olanzapine in primary care settings in the United States. It was found that olanzapine was marketed off-label in primary care settings for relatively mild symptoms that were framed as bipolar disorder and schizophrenia. A key strategy in this campaign was the use of hypothetical patient profiles in detailing visits, most of which clearly failed to meet diagnostic criteria for any recognized mental disorder. Evidence emerged that olanzapine was also marketed off-label as a treatment for dementia.

  8. Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia

    Directory of Open Access Journals (Sweden)

    Hong J

    2013-09-01

    Full Text Available Jihyung Hong,1 Diego Novick,1 Tamás Treuer,2 William Montgomery,3 Virginia S Haynes,4 Shenghu Wu,5 Josep Maria Haro61Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly and Company, Neuroscience Research, Budapest, Hungary; 3Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 4Eli Lilly and Company, Indianapolis, IN, US; 5Eli Lilly China, Shanghai, People's Republic of China; 6Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, SpainPurpose: To assess baseline predictors and consequences of medication non-adherence in the treatment of pediatric patients with attention-deficit/hyperactivity disorder (ADHD from Central Europe and East Asia.Patients and methods: Data for this post-hoc analysis were taken from a 1-year prospective, observational study that included a total of 1,068 newly-diagnosed pediatric patients with ADHD symptoms from Central Europe and East Asia. Medication adherence during the week prior to each visit was assessed by treating physicians using a 5-point Likert scale, and then dichotomized into either adherent or non-adherent. Clinical severity was measured by the Clinical Global Impressions-ADHD-Severity (CGI-ADHD scale and the Child Symptom Inventory-4 (CSI-4 Checklist. Health-Related Quality of Life (HRQoL was measured using the Child Health and Illness Profile-Child Edition (CHIP-CE. Regression analyses were used to assess baseline predictors of overall adherence during follow-up, and the impact of time-varying adherence on subsequent outcomes: response (defined as a decrease of at least 1 point in CGI, changes in CGI-ADHD, CSI-4, and the five dimensions of CHIP-CE.Results: Of the 860 patients analyzed, 64.5% (71.6% in Central Europe and 55.5% in East Asia were rated as adherent and 35.5% as non-adherent during follow-up. Being from East Asia was found to be a strong predictor of non-adherence. In East Asia, a family history of ADHD and parental emotional

  9. 2008. aasta tõlkeilukirjandus / Kätlin Kaldmaa

    Index Scriptorium Estoniae

    Kaldmaa, Kätlin, 1970-

    2009-01-01

    Ülevaade 2008. aastal Eestis ilmunud tõlkeilukirjandusest. Pikemalt käsitletakse järgmisi autoreid ja nende teoseid: Margaret Atwood "Ebakõlad", William Faulkner "Absalom! Absalom!", Cormac McCarthy "Tee", Halldór Laxness "Islandi kell", T. H. White "Kunagine ja tulevane kuningas", Guillermo Martínez "Märkamatud mõrvad", Charlotte Weitze "Pimeduse pärusmaa", Daniel Kehlmann "Maailma mõõtmine", Milorad Pavić "Tuule sisemine pool, ehk, Romaan Herost ja Leandrosest", Michel Houellebecq "Elementaarosakesed", Marguerite Duras "Põhja-Hiina armuke", Haruki Murakami "Kafka mererannas", Anne Birkefeldt Radge "Berliini paplid", "Erakvähid" ja "Rohelised aasad", Linn Ullmann "Õnnistatud laps", Lars Saabye Christensen "Modell", Jon Fosse "See on Ales", Peter Høeg "Vaikne tüdruk", Leena Krohn "Matemaatilised olendid", Käbi Laretei "Kuhu kadus kõik see armastus?", E. M. Forster "Teekond Indiasse", Rudyard Kipling "Lispeth", Asha Miró ja Anna Soler-Pont "Sandlipuu jäljed", Khaled Hosseini "Lohejooksja", Billy Collins "Allegooria surm", Wisława Szymborska "Oma aja lapsed", Zbigniew Herbert "Valitud luuletused", Carlos Vitale "Kohaühtsus", Jüri Talvet (koostaja) "Ameerika luule antoloogia", Marjane Satrapi "Persepolis", Hergé "Sinine lootos" ja "Vaarao sigar", Sinikka Nopola "Risto Räppar ja kohutav vorst" ja "Risto Räppar ja viimane hoiatus", Espen Fyksen ja Øyvind Rune Stålen "Elias, väike päästekaater", Hannu Mäkelä "Miisa uus pere", Timo Parvela "Kiigelaud", Nick Hornby "Maoli", Pierre Bayard "Kuidas rääkida raamatutest, mida me pole lugenud", Milan Kundera "Eesriie", Georges Perec "Mõelda/liigitada ja teisi tekste"

  10. 2008. aasta tõlkeilukirjandus / Kätlin Kaldmaa

    Index Scriptorium Estoniae

    Kaldmaa, Kätlin, 1970-

    2009-01-01

    Ülevaade 2008. aastal Eestis ilmunud tõlkeilukirjandusest. Pikemalt käsitletakse järgmisi autoreid ja nende teoseid: Margaret Atwood "Ebakõlad", William Faulkner "Absalom! Absalom!", Cormac McCarthy "Tee", Halldór Laxness "Islandi kell", T. H. White "Kunagine ja tulevane kuningas", Guillermo Martínez "Märkamatud mõrvad", Charlotte Weitze "Pimeduse pärusmaa", Daniel Kehlmann "Maailma mõõtmine", Milorad Pavić "Tuule sisemine pool, ehk, Romaan Herost ja Leandrosest", Michel Houellebecq "Elementaarosakesed", Marguerite Duras "Põhja-Hiina armuke", Haruki Murakami "Kafka mererannas", Anne Birkefeldt Radge "Berliini paplid", "Erakvähid" ja "Rohelised aasad", Linn Ullmann "Õnnistatud laps", Lars Saabye Christensen "Modell", Jon Fosse "See on Ales", Peter Høeg "Vaikne tüdruk", Leena Krohn "Matemaatilised olendid", Käbi Laretei "Kuhu kadus kõik see armastus?", E. M. Forster "Teekond Indiasse", Rudyard Kipling "Lispeth", Asha Miró ja Anna Soler-Pont "Sandlipuu jäljed", Khaled Hosseini "Lohejooksja", Billy Collins "Allegooria surm", Wisława Szymborska "Oma aja lapsed", Zbigniew Herbert "Valitud luuletused", Carlos Vitale "Kohaühtsus", Jüri Talvet (koostaja) "Ameerika luule antoloogia", Marjane Satrapi "Persepolis", Hergé "Sinine lootos" ja "Vaarao sigar", Sinikka Nopola "Risto Räppar ja kohutav vorst" ja "Risto Räppar ja viimane hoiatus", Espen Fyksen ja Øyvind Rune Stålen "Elias, väike päästekaater", Hannu Mäkelä "Miisa uus pere", Timo Parvela "Kiigelaud", Nick Hornby "Maoli", Pierre Bayard "Kuidas rääkida raamatutest, mida me pole lugenud", Milan Kundera "Eesriie", Georges Perec "Mõelda/liigitada ja teisi tekste"

  11. Ketamine: stimulating antidepressant treatment?

    Science.gov (United States)

    Malhi, Gin S; Byrow, Yulisha; Cassidy, Frederick; Cipriani, Andrea; Demyttenaere, Koen; Frye, Mark A; Gitlin, Michael; Kennedy, Sidney H; Ketter, Terence A; Lam, Raymond W; McShane, Rupert; Mitchell, Alex J; Ostacher, Michael J; Rizvi, Sakina J; Thase, Michael E; Tohen, Mauricio

    2016-05-01

    The appeal of ketamine - in promptly ameliorating depressive symptoms even in those with non-response - has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives - derived from evidence and clinical experience - and to consider strategies for future investigations. G.S.M. Grant/research support: National Health Medical Research Council, NSW Health, Ramsay Health, American Foundation for Suicide Prevention, AstraZeneca, Eli Lilly & Co, Organon, Pfizer, Servier, and Wyeth; has been a speaker for Abbott, AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth; consultant: AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and Servier. M.A.F. Grant support: AssureRx, Janssen Research & Development, Mayo Foundation, Myriad, National Institute of Alcohol Abuse and Alcoholism (NIAAA), National Institute of Mental Health (NIMH), Pfizer. Consultant (Mayo): Janssen Research & Development, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad Genetics, Neuralstem Inc., Sunovion, Supernus Pharmaceuticals, Teva Pharmaceuticals. CME/travel support: American Physician Institute, CME Outfitters. Financial interest/Mayo Clinic 2016: AssureRx. S.H.K. Grant/research support: Brain Canada, Bristol Meyer Squibb, CIHR, Janssen, Johnson & Johnson, Lundbeck, Ontario Brain Institute, Pfizer, Servier, St. Jude Medical, Sunovion. T.A.K. Grant/research support (through Stanford University): Sunovion Pharmaceuticals and Merck & Co., Inc.; consultant/advisory board bember: Allergan, Inc., Janssen Pharmaceuticals, Myriad Genetic Laboratories, Inc., and Sunovion Pharmaceuticals; lecture honoraria (not Speaker's Bureau payments): Glaxo

  12. Usability of a novel disposable autoinjector device for ixekizumab: results from a qualitative study and an open-label clinical trial, including patient-reported experience

    Directory of Open Access Journals (Sweden)

    Callis Duffin K

    2016-10-01

    Full Text Available Kristina Callis Duffin,1 Michael Bukhalo,2 Margaret A Bobonich,3 David Shrom,4 Fangyi Zhao,4 James R Kershner,4 Anne Gill,4 Beth Pangallo,4 Catherine L Shuler,4 Jerry Bagel5 1Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, 2Arlington Dermatology, Arlington Heights, IL, 3CWRU Schools of Medicine and Nursing, Case Western Reserve University Cleveland, OH, 4Lilly Research Labs, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 5Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ, USA Background: Most biologic therapies for psoriasis are delivered via subcutaneous injection. Ixekizumab, an anti-interleukin 17A monoclonal antibody approved for patients with moderate-to-severe plaque psoriasis, is delivered subcutaneously via prefilled syringe or autoinjector. Here we report the results of an ixekizumab autoinjector usability study as well as the patient-reported experience with the autoinjector in a clinical trial. Methods: The usability study enrolled 49 subjects (patients with a range of autoimmune conditions or their caregivers. Subjects were randomized to a trained or untrained group and were evaluated for their ability to perform an injection successfully when provided the device and the instructions for use. In the clinical trial, 102 subjects (patients with psoriasis or their caregivers used the autoinjector to deliver injections of ixekizumab (80 mg every 2 weeks after a starting dose of 160 mg. At weeks 0, 4, and 8, subjects completed the subcutaneous administration assessment questionnaire, which assesses the ease of use and confidence with using an injection device. Results: In the usability study, all subjects in the untrained arm performed successful injections, while two subjects in the trained arm had an injection failure. These incidences were not consistent with any pattern of issues with the device or the instructions for use. In the clinical trial, there were two

  13. Estimating the real world daily usage and cost for exenatide twice daily and liraglutide in Germany, the Netherlands, and the UK based on volumes dispensed by pharmacies

    Directory of Open Access Journals (Sweden)

    McDonell AL

    2015-01-01

    Full Text Available Amanda L McDonell,1 Urpo Kiiskinen,2 Danielle C Zammit,3 Robert W Kotchie,1 Per-Olof Thuresson,3 Claudia Nicolay,4 Thomas Haslam,1 Michiel Bruinsma,5 Anne-Jeanine Janszen-Van Oosterhout,6 Thorsten Otto41IMS Health, London, UK; 2Eli Lilly and Company, Helsinki, Finland; 3IMS Health, Basel, Switzerland; 4Eli Lilly and Company, Bad Homburg, Germany; 5IMS Health, Rotterdam, the Netherlands; 6Eli Lilly Nederland, Houten, the NetherlandsBackground: Glucagon-like peptide-1 (GLP-1 receptor agonists are indicated for improvement of glycemic control in adults with type 2 diabetes. Cost is one aspect of treatment to be considered, in addition to clinical benefits, when selecting optimal therapy for a patient. The objective of this study was to estimate the average dose usage and real world daily cost of the GLP-1 receptor agonists, exenatide twice daily and liraglutide once daily, in Germany, the Netherlands, and the UK.Methods: Administrative databases were used to source the data from longitudinal records of dispensed prescriptions. Data were extracted from the IMS Longitudinal Prescription database which captures details of prescriptions dispensed in pharmacies. Information on the dispensed quantity of each product was used to estimate average daily usage per patient. Daily dose usage was multiplied by the public price per unit to estimate daily cost.Results: The dispensed volume in Germany corresponded to a mean dispensed daily dose of 16.81 µg for exenatide twice daily and 1.37 mg for liraglutide (mean daily cost €4.02 and €4.54, respectively. In the Netherlands, average dispensed daily doses of 17.07 µg and 1.49 mg were observed for exenatide twice daily and liraglutide (mean daily cost €3.05 and €3.97, respectively. In the UK, the mean dispensed volume corresponded to a daily usage of 20.49 µg for exenatide twice daily and 1.50 mg for liraglutide (mean daily cost £2.53 and £3.28, respectively.Conclusion: Estimates of average daily

  14. Treatment discontinuation and tolerability as a function of dose and titration of duloxetine in the treatment of major depressive disorder

    Directory of Open Access Journals (Sweden)

    Harada E

    2016-01-01

    Full Text Available Eiji Harada,1 Osamu Shirakawa,2 Yoichi Satoi,3 Lauren B Marangell,4 Rodrigo Escobar5 1Eli Lilly Japan K.K., Medicines Development Unit Japan, Medical Science, Kobe, 2Department of Neuropsychiatry, Kinki University Faculty of Medicine, Osakasayama, 3Eli Lilly Japan K.K., Medicines Development Unit Japan, Statistical Science, Kobe, Japan; 4The University of Texas Health Science Center School of Medicine, Houston, TX, 5Eli Lilly and Company, Neuroscience, Indianapolis, IN, USA Purpose: We sought to better understand how dose and titration with duloxetine treatment may impact tolerability and treatment discontinuation in patients with major depressive disorder.Patients and methods: We investigated Phase III duloxetine trials. Group 1 was a single placebo-controlled study with a 20 mg initial dose and a slow titration to 40 and 60 mg. Group 2 was a single study with a 40 mg initial dose and final “active” doses of 40 and 60 mg (5 mg control group, with 1-week titration. Group 3 consisted of eight placebo-controlled studies with starting doses of 40, 60, and 80 mg/day with minimal titration (final dose 40–120 mg/day. Tolerability was measured by rate of discontinuation due to adverse events (DCAE.Results: The DCAE in Group 1 were 3.6% in the 60 mg group, 3.3% in the 40 mg group, and 3.2% in the placebo group. In Group 2, the DCAE were 15.0% in the 60 mg group, 8.1% in the 40 mg group, and 4.9% in the 5 mg group. In Group 3, the DCAE were 9.7% and 4.2% in the duloxetine and placebo groups, respectively.Conclusion: This study suggests that starting dose and titration may have impacted tolerability and treatment discontinuation. A lower starting dose of duloxetine and slower titration may contribute to improving treatment tolerability for patients with major depressive disorder. Keywords: antidepressant, dose, duloxetine, major depressive disorder, titration

  15. A review of the efficacy of atomoxetine in the treatment of attention-deficit hyperactivity disorder in children and adult patients with common comorbidities

    Directory of Open Access Journals (Sweden)

    Clemow DB

    2017-02-01

    Full Text Available David B Clemow,1 Chris Bushe,2 Michele Mancini,3 Michael H Ossipov,4 Himanshu Upadhyaya1 1Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly, Windlesham, UK; 3Eli Lilly Italia S.p.A., Sesto Fiorentino, Italy; 4inVentiv Health Clinical, LLC, Blue Bell, PA, USA Abstract: Attention-deficit hyperactivity disorder (ADHD is a common neuropsychiatric disorder that is often diagnosed during childhood, but has also increasingly been recognized to occur in adults. Importantly, up to 52% of children (including adolescents and 87% of adults with ADHD also have a comorbid psychiatric disorder. The presence of a comorbid disorder has the potential to impact diagnosis and could affect treatment outcomes. Atomoxetine is a nonstimulant treatment for ADHD. Despite numerous published studies regarding efficacy of atomoxetine in the treatment of ADHD in patients with comorbid disorders, there is limited information about the impact of individual common comorbid disorders on the efficacy of atomoxetine for ADHD, especially with regard to adults. Moreover, a cumulative review and assessment of these studies has not been conducted. For this reason, we performed a literature review to find, identify, and cumulatively review clinical studies that examined the efficacy of atomoxetine in the treatment of patients with ADHD and comorbid psychiatric disorders. We found a total of 50 clinical studies (37 in children; 13 in adults that examined the efficacy of atomoxetine in patients with ADHD and a comorbid disorder. The comorbidities that were studied in children or in adults included anxiety, depression, and substance use disorder. Overall, the presence of comorbidity did not adversely impact the efficacy of atomoxetine in treatment of ADHD symptoms in both patient populations. In the studies identified and assessed in this review, atomoxetine did not appear to exacerbate any of the comorbid conditions and could, therefore, be an important therapy choice for the

  16. Why study lakes? An overview of USGS lake studies in Wisconsin

    Science.gov (United States)

    Garn, Herbert S.; Elder, J.F.; Robertson, D.M.

    2003-01-01

    Wisconsin’s 15,000 lakes are prominent features in its landscape and an important public resource. In the northern part of the State, the recent glaciation (ending about 10,000 years ago) created one of the densest clusters of lakes found anywhere in the world, containing lakes that occupy depressions in the glacial moraines and outwash deposits (fig. 1). This Northern Lakes and Forests Ecoregion contains more than 80 percent of the State’s lakes (Wisconsin Department of Natural Resources, 2001). South of this ecoregion, there are fewer lakes, but they still are common. Usually situated in agricultural or urban land- scapes, lakes in southern Wisconsin generally have higher levels of nutrients and alkalinity, and higher biological productivity than their northern counterparts. For most lakes in Wisconsin, phosphorus is the nutrient that limits algal growth (Lillie and Mason, 1983).

  17. Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

    Directory of Open Access Journals (Sweden)

    Novick D

    2015-01-01

    Full Text Available Diego Novick,1 Jihyung Hong,1 William Montgomery,2 Héctor Dueñas,3 Magdy Gado,4 Josep Maria Haro5 1Eli Lilly and Company, Windlesham, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, Australia; 3Eli Lilly de Mexico, Mexico City, Mexico; 4Eli Lilly and Company, Riyadh, Saudi Arabia; 5Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain Background: This study examined potential predictors of remission among patients treated for major depressive disorder (MDD in a naturalistic clinical setting, mostly in the Middle East, East Asia, and Mexico. Methods: Data for this post hoc analysis were taken from a 6-month prospective, noninterventional, observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in 12 countries worldwide. Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16. Depression-related pain was measured using the pain-related items of the Somatic Symptom Inventory. Remission was defined as a QIDS-SR16 score ≤5. Generalized estimating equation regression models were used to examine baseline factors associated with remission during follow-up. Results: Being from East Asia (odds ratio [OR] 0.48 versus Mexico; P<0.001, a higher level of depression severity at baseline (OR 0.77, P=0.003, for Clinical Global Impression of Severity; OR 0.92, P<0.001, for QIDS-SR16, more previous MDD episodes (OR 0.92, P=0.007, previous treatments/therapies for depression (OR 0.78, P=0.030, and having any significant psychiatric and medical comorbidity at baseline (OR 0.60, P<0.001 were negatively associated with remission, whereas being male (OR 1.29, P=0.026 and treatment with duloxetine (OR 2.38 versus selective serotonin reuptake inhibitors, P<0.001 were positively associated with remission. However, the association between Somatic Symptom Inventory pain scores

  18. LES of Turbulent Flows Through a Butterfly Valve

    Science.gov (United States)

    Gong, J. F.; Ming, P. J.; Zhang, W. P.

    2011-09-01

    Large-eddy simulation (LES) is used to analyze the wake flow characteristics around a butterfly valve. The Smagorinsky- Lilly (SML) model is used for the investigation. The turbulent fluctuations and power spectrum of the wake flow are analyzed for Re = 5.23 × 105 based on the mean inlet velocity and the diameter of the pipe. Four dominating frequencies corresponding to the Strouhal number equal to 0.084, 0.114, 0.152 and 0.175 are found both in the near-wall region and in the midst of the pipe. The evolution of vortices around the valve is presented to illustrate the formation of the single vortex propagating downstream.

  19. Tikutõmbeid kottpimedas galeriis = Striking matches in a pitch-dark gallery : [luuletused] / Artur Alliksaar

    Index Scriptorium Estoniae

    Alliksaar, Artur, 1923-1966

    2001-01-01

    Tekst eesti ja inglise k. A. Alliksaare lühibiograafia eesti ja inglise k. lk. 55. Sisu: Tikutõmbeid kottpimedas galeriis = Striking matches in a pitch-dark gallery ; "Olen määratusuur mets..." = "I am infinitely vast forest..." ; "Olen koredate külgedega kalju..." = "I am rough-sided cliff..." ; "Olen meri, millel puudub äär..." = "I am sea that knows no bounds..." ; "Liikumine on niivõrd liitunud mu loomusega..." = "Movement is so much part of me..." ; "Ma ei söandaks öelda, et olen rikas..." = "I would not claim that I am rich..." ; Pöördehetk = Turning point ; Kuigi on nii palju lilli... = Though there are so many flowers ; Antidolorosum

  20. Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (prozac)

    DEFF Research Database (Denmark)

    Andersen, Jacob; Stuhr-Hansen, Nicolai; Zachariassen, Linda Grønborg

    2014-01-01

    , and computational methods to decipher the molecular basis for high-affinity recognition in SERT and selectivity over NET for the prototypical antidepressant drug fluoxetine (Prozac; Eli Lilly, Indianapolis, IN). We show that fluoxetine binds within the central substrate site of human SERT, in agreement with recent...... X-ray crystal structures of LeuBAT, an engineered monoamine-like version of the bacterial amino acid transporter LeuT. However, the binding orientation of fluoxetine is reversed in our experimentally supported model compared with the LeuBAT structures, emphasizing the need for careful experimental...... verification when extrapolating findings from crystal structures of bacterial transporters to human relatives. We find that the selectivity of fluoxetine and nisoxetine, a NET selective structural congener of fluoxetine, is controlled by residues in different regions of the transporters, indicating a complex...

  1. Cardiovascular Side Effects of Atomoxetine and Its Interactions with Inhibitors of the Cytochrome P450 System

    Directory of Open Access Journals (Sweden)

    Pashtoon Murtaza Kasi

    2011-01-01

    Full Text Available Attention deficit hyperactivity disorder (ADHD is one of the most common neurobehavioral disorders of childhood and adolescence. Classically, stimulants have been used in the treatment of this condition. Atomoxetine (Strattera; Eli Lilly and Company is a selective norepinephrine reuptake inhibitor (SNRI, one of the first medications in the nonstimulant class of medications that has been approved by the FDA for the treatment of ADHD. Atomoxetine is a phenoxypropylamine derivative and is structurally related to the antidepressant fluoxetine. The common side effects reported with the use of atomoxetine include mainly GI disturbances. Cardiovascular side effects are less commonly reported. The increase in the noradrenergic tone may explain some of the side effects noted with the use of this medication. Here, we present a case of a patient who presented with syncope, orthostatic hypotension, and tachycardia and discuss the various clinical implications based on the pharmacokinetics and pharmacodynamics of the drug.

  2. Measuring the effectiveness and impact of an open innovation platform.

    Science.gov (United States)

    Carroll, Glenn P; Srivastava, Sanjay; Volini, Adam S; Piñeiro-Núñez, Marta M; Vetman, Tatiana

    2017-01-27

    Today, most pharmaceutical companies complement their traditional R&D models with some variation on the Open Innovation (OI) approach in an effort to better access global scientific talent, ideas and hypotheses. Traditional performance indicators that measure economic returns from R&D through commercialization are often not applicable to the practical assessment of these OI approaches, particularly within the context of early drug discovery. This leaves OI programs focused on early R&D without a standard assessment framework from which to evaluate overall performance. This paper proposes a practical dashboard for such assessment, encompassing quantitative and qualitative elements, to enable decision-making and improvement of future performance. The use of this dashboard is illustrated using real-time data from the Lilly Open Innovation Drug Discovery (OIDD) program.

  3. Industrial demand side management: A status report

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.F.; Conger, R.L.; Foley, T.J. [and others

    1995-05-01

    This report provides an overview of and rationale for industrial demand side management (DSM) programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential energy savings in kilowatt hours. The report presents types and examples of programs and explores elements of successful programs. Two in-depth case studies (from Boise Cascade and Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. A comprehensive bibliography is included, technical assistance programs are listed and described, and a methodology for evaluating potential or actual savings from projects is delineated.

  4. Functioning in patients with major depression treated with duloxetine or a selective serotonin reuptake inhibitor in East Asia

    Directory of Open Access Journals (Sweden)

    Novick D

    2016-02-01

    Full Text Available Diego Novick,1 William Montgomery,2 Josep Maria Haro,3 Maria Victoria Moneta,3 Gang Zhu,4 Li Yue,5 Jihyung Hong,6 Héctor Dueñas,7 Roberto Brugnoli8 1Eli Lilly and Company, Windlesham, Surrey, UK; 2Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia; 3Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, CIBERSAM, Universitat de Barcelona, Barcelona, Spain; 4Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, 5Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People’s Republic of China; 6Department of Healthcare Management, Gachon University, Seongnam, South Korea; 7Eli Lilly de Mexico, Mexico City, Mexico; 8School of Medicine, Sapienza University of Rome, Rome, ItalyPurpose: To assess and compare the levels of functioning in patients with major depressive disorder treated with either duloxetine with a daily dose of ≤60 mg or a selective serotonin reuptake inhibitor (SSRI as monotherapy for up to 6 months in a naturalistic setting in East Asia. In addition, this study examined the impact of painful physical symptoms (PPS on the effects of these treatments.Patients and methods: Data for this post hoc analysis were taken from a 6-month prospective observational study involving 1,549 patients with major depressive disorder without sexual dysfunction. The present analysis focused on a subgroup of patients from East Asia (n=587. Functioning was measured using the Sheehan Disability Scale (SDS. Depression severity was assessed using the 16-item Quick Inventory of Depressive Symptomatology-Self Report. PPS were rated using the modified Somatic Symptom Inventory. A mixed model with repeated measures was fitted to compare the levels of functioning between duloxetine-treated (n=227 and SSRI-treated (n=225 patients, adjusting for baseline patient characteristics.Results: The mean SDS total score was similar between the two treatment cohorts (15.46 [standard deviation =6.11] in the duloxetine

  5. Tikutõmbeid kottpimedas galeriis = Striking matches in a pitch-dark gallery : [luuletused] / Artur Alliksaar

    Index Scriptorium Estoniae

    Alliksaar, Artur, 1923-1966

    2001-01-01

    Tekst eesti ja inglise k. A. Alliksaare lühibiograafia eesti ja inglise k. lk. 55. Sisu: Tikutõmbeid kottpimedas galeriis = Striking matches in a pitch-dark gallery ; "Olen määratusuur mets..." = "I am infinitely vast forest..." ; "Olen koredate külgedega kalju..." = "I am rough-sided cliff..." ; "Olen meri, millel puudub äär..." = "I am sea that knows no bounds..." ; "Liikumine on niivõrd liitunud mu loomusega..." = "Movement is so much part of me..." ; "Ma ei söandaks öelda, et olen rikas..." = "I would not claim that I am rich..." ; Pöördehetk = Turning point ; Kuigi on nii palju lilli... = Though there are so many flowers ; Antidolorosum

  6. Suicidality and aggression during antidepressant treatment

    DEFF Research Database (Denmark)

    Sharma, Tarang; Guski, Louise Schow; Freund, Nanna;

    2016-01-01

    reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly's website.Eligibility criteria for study selection Double blind placebo controlled trials that contained any....... These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any......Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.Design Systematic review and meta-analysis.Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.Data sources Clinical study...

  7. Interview with Lisa Shipley. Interviewed by Lisa Parks.

    Science.gov (United States)

    Shipley, Lisa

    2013-08-01

    Lisa Shipley is Vice President of Pharmacokinetics, Pharmacodynamics and Drug Metabolism at Merck Research Laboratories. She is responsible for preclinical and clinical ADME activities and molecular biomarker assay development activities at all Merck research sites and support of all programs from discovery through to post-product launch. Prior to joining Merck in 2008, Shipley spent over 20 years at Eli Lilly and Company in roles of increasing responsibility, including the positions of executive director at Lean Six Sigma and vice president of Drug Disposition, PK/PD and Trial Simulations. Shipley obtained her undergraduate degree from McDaniel College and her doctoral degree in Pharmacology and Toxicology from the University of Maryland at Baltimore. This interview was conducted by Lisa Parks, Assistant Commissioning Editor of Bioanalysis.

  8. The insulin secretory action of novel polycyclic guanidines: discovery through open innovation phenotypic screening, and exploration of structure-activity relationships.

    Science.gov (United States)

    Shaghafi, Michael B; Barrett, David G; Willard, Francis S; Overman, Larry E

    2014-02-15

    We report the discovery of the glucose-dependent insulin secretogogue activity of a novel class of polycyclic guanidines through phenotypic screening as part of the Lilly Open Innovation Drug Discovery platform. Three compounds from the University of California, Irvine, 1-3, having the 3-arylhexahydropyrrolo[1,2-c]pyrimidin-1-amine scaffold acted as insulin secretagogues under high, but not low, glucose conditions. Exploration of the structure-activity relationship around the scaffold demonstrated the key role of the guanidine moiety, as well as the importance of two lipophilic regions, and led to the identification of 9h, which stimulated insulin secretion in isolated rat pancreatic islets in a glucose-dependent manner. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Inhaled insulin for controlling blood glucose in patients with diabetes

    Directory of Open Access Journals (Sweden)

    Bernard L Silverman

    2008-01-01

    Full Text Available Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

  10. Udvikling af studerendes akademiske skrivekompetencer – en indsats på fakultetsniveau

    DEFF Research Database (Denmark)

    Jensen, Tine Wirenfeldt; Andersen, Per

    ." Studies in higher education 23.2 (1998): 157-172. Russell, David R. Writing in the Academic Disciplines, 1870-1990: A Curricular History. Southern Illinois University Press, (1991). Wingate, Ursula. "Doing away with ‘study skills’." Teaching in Higher Education. 11.4 (2006): 457-469. Murphy, Christina...... og perspektiver på akademisk skrivning. Særlige temaer udpeges som fremtidige indsatsområder (fx på baggrund af de studerendes oplevelser med brugen af peer feedback i undervisningen). Referencer Lea, Mary R., and Brian V. Street. "Student writing in higher education: An academic literacies approach......, and Joe Law. Landmark essays on writing centers. Vol. 9. Routledge, (2013). Gillespie, Paula, et al., eds. Writing center research: Extending the conversation. Routledge, (2001). Lillis, Theresa, and Joan Turner. "Student writing in higher education: contemporary confusion, traditional concerns." Teaching...

  11. Virtual screening and repositioning of inconclusive molecules of beta-lactamase Bioassays-A data mining approach.

    Science.gov (United States)

    Gad, Akshata; Manuel, Andrew Titus; K R, Jinuraj; John, Lijo; R, Sajeev; V G, Shanmuga Priya; U C, Abdul Jaleel

    2017-07-29

    This study focuses on the best possible way forward in utilizing inconclusive molecules of PubChem bioassays AID 1332, AID 434987 and AID 434955, which are related to beta-lactamase inhibitors of Mycobacterium tuberculosis (Mtb). The inadequacy in the experimental methods that were observed during the invitro screening resulted in an inconclusive dataset. This could be due to certain moieties present within the molecules. In order to reconsider such molecules, insilico methods can be suggested in place of invitro methods For instance, datamining and medicinal chemistry methods: have been adopted to prioritise the inconclusive dataset into active or inactive molecules. These include the Random Forest algorithm for dataminning, Lilly MedChem rules for virtually screening out the promiscuity, and Self Organizing Maps (SOM) for clustering the active molecules and enlisting them for repositioning through the use of artificial neural networks. These repositioned molecules could then be prioritized for downstream drug discovery analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Large eddy simulation of hot and cold fluids mixing in a T-junction for predicting thermal fluctuations

    Institute of Scientific and Technical Information of China (English)

    Wei-yu ZHU; Tao LU; Pei-xue JIANG; Zhi-jun GUO; Kui-sheng WANG

    2009-01-01

    Temperature fluctuations in a mixing T-junction have been simulated on the FLUENT platform using the large eddy simulation (LES) turbulent flow model and a sub-grid scale Smagorinsky-Lilly model. The normalized mean and root mean square temperatures for describing time-averaged temperature and temperature fluctuation intensity, and the velocity are obtained. The power spectrum densities of temperature fluctuations, which are key parameters for thermal fatigue analysis and lifetime evaluation, are analyzed. Simulation results are consistent with experimental data published in the literature, showing that the LES is reliable. Several mixing processes under different conditions are simulated in order to analyze the effects of varying Reynolds number and Richardson number on the mixing course and thermal fluctuations.

  13. A Family Case Study: How Money Might Matter for Academic Learning

    Directory of Open Access Journals (Sweden)

    Catherine Compton - Lilly

    2014-04-01

    Full Text Available Many children living in low income communities do not face struggles in school. Many learn quickly and easily. But for some students, living in a high poverty communities and attending underfunded schools has consequences that can make learning difficult. In this paper, Compton-Lilly draws on the words of a parent living in a low-income community to explore how economic and social challenges affected the schooling of her daughter over a ten-year period. As the following accounts reveal, Ms. Rodriguez, an African American, low-income parent, was committed to her daughter’s learning and school progress and brought a thoughtful and informed critique to her children’s school experience that reveals the multiple ways that money affects academic learning.

  14. Strategies for conducting ADME studies during lead generation in the drug discovery process.

    Science.gov (United States)

    Cramer, Jeffrey W; Mattioni, Brian E; Savin, Kenneth A

    2010-12-01

    Although the benefit of early ADME screening is widely recognized in the pharmaceutical industry, the implementation of this paradigm is often performed with insufficient resources and poor collaboration between functions. Dedicated and consistent integration efforts of ADME knowledge during the lead generation (LG) phase of drug discovery enables informed resourcing decisions and also increases the quality of initial starting points for discovery projects. To facilitate the efficient and consistent application of ADME resources to early projects at Eli Lilly and Co, a team of scientists was formed to provide dedicated ADME support to the LG phase of the discovery portfolio. This feature review discusses the working construct of the team, the general philosophy that was employed, and the outcomes of this endeavor.

  15. [Giemsa stain's 100th year].

    Science.gov (United States)

    Perea-Sasiaín, José

    2003-03-01

    Research work associated with the development of Giemsa stain is revived, with emphasis on the methylene blue polychromes. A short biographical sketch of Dr. Berthold Gustav Carl Giemsa is presented, along with the composition of his original formulation and its mec. HPLC analyses of his azur II indicated the following composition: methylene blue 63.6%, azur B 28.6%, azur A 4.4%, azur C 1.4%, thionin 1.9%. Azur I was not "pure", but rather a mixture of thionin and all of its 3 and 7 N-methylated derivatives. Lillie inferred that it was probably prepared by an acid oxidation process. Applications of Giemsa stain reported in the last 32 years are tabulated.

  16. 大涡模拟搅拌槽内混合时间%Large Eddy Simulations of Mixing Time in a Stirred Tank

    Institute of Scientific and Technical Information of China (English)

    闵健; 高正明

    2006-01-01

    Large eddy simulations (LES) of mixing process in a stirred tank of 0.476m diameter with a 3-narrow blade hydrofoil CBY impeller were reported. The turbulent flow field and mixing time were calculated using LES with Smagorinsky-Lilly subgrid scale model. The impeller rotation was modeled using the sliding mesh technique. Better agreement of power demand and mixing time was obtained between the experimental and the LES prediction than that by the traditional Reynolds-averaged Navier-Stokes (RANS) approach. The curve of tracer response predicted by LES was in good agreement with the experimental. The results show that LES is a reliable tool to investigate the unsteady and quasi-periodic behavior of the turbulent flow in stirred tanks.

  17. Influence of stable stratification on three-dimensional isotropic turbulence

    Science.gov (United States)

    Metais, O.

    The influence of a stable stratification on three-dimensional homogeneous turbulence is investigated by performing large eddy simulations with the subgrid scales procedure developed by Chollet and Lesieur for isotropic turbulence. Computational initial conditions close to those of the experiments performed by Itsweire, Helland and Van Atta allow the comparison of the experimental and numerical evolutions of density-stratified turbulent flows. Theoretical works by Riley, Metcalfe and Weisman and by Lilly suggest that low Froude number stably-stratified turbulence may be a nearly noninteracting superposition of wave and quasi-horizontal turbulent vortex motions. For our computations the stably-stratified turbulence seems to be a decaying three-dimensional turbulence pulsed by internal gravity waves. However some tendencies towards two-dimensional turbulence are observed.

  18. Measurement and simulation of swirling coal combustion

    Institute of Scientific and Technical Information of China (English)

    Liyuan Hu; Lixing Zhou; Yonghao Luo; Caisong Xu

    2013-01-01

    Particle image velocimetry (PIV),thermocouples and flue gas analyzer are used to study swirling coal combustion and NO formation under different secondary-air ratios.Eulerian-Lagrangian large-eddy simulation (LES) using the Smagorinsky-Lilly sub-grid scale stress model,presumed-PDF fast chemistry and eddy-break-up (EBU) gas combustion models,particle devolatilization and particle combustion models,are simultaneously used to simulate swirling coal combustion.Statistical LES results are validated by measurement results.Instantaneous LES results show that the coherent structures for swirling coal combustion are stronger than those for swirling gas combustion.Particles are shown to concentrate along the periphery of the coherent structures.Combustion flame is located in the high vorticity and high particle concentration zones.Measurement shows that secondary-air ratios have little effect on final NO formation at the exit of the combustor.

  19. A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

    Directory of Open Access Journals (Sweden)

    Taipale K

    2017-08-01

    Full Text Available Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS and overall survival (OS relative to gemcitabine + cisplatin (induction sequences or best supportive care (BSC (maintenance sequences. Modeled health-care benefits were expressed as life-years (LYs and quality-adjusted LYs (QALYs (estimated using French EuroQol five-dimension questionnaire tariffs. The study was conducted from the payer perspective (National Health Insurance. Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed

  20. 研究显示每周服用一次Exenatide可比Lantus更好控制血糖

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Amylin制药公司、Eli Lilly and Company公司和Alkermes公司宣布了一项临床研究的可喜阳性结果,此项研究用随机的方式让患者每周服用一次exenatide(Ⅰ)或服用Lantus(insulin glargine)(Ⅱ),并比较其疗效差异。AIC(糖化血红蛋白)在较长时间内(超过三个月)可以衡量平均血糖,在此项研究中将其作为平均血糖的衡量指标。经过26周的治疗,

  1. The Antidiabetics Market: Tendencies and Research Directions

    Directory of Open Access Journals (Sweden)

    Claudiu MOROGVAN

    2010-03-01

    Full Text Available Diabetes mellitus is a pathology with multiple and severe implications. Its prevalence has been continuously increasing during the last years, as well as the number of drugs introduced in its therapy. The value of the antidiabetics global market was evaluated at over 18 billion USD in 2005. The following five international producers hold the biggest share: NovoNordisk, Takeda, Sanofi-Aventis, GlaxoSmithkline and Eli Lilly. The two bestselling drugs in the USA in 2008 were Actos and Lantus, two products of latest generation, which, however, seems to be a global tendency. As far as the OAD (Oral Antidiabetic Drug category is concerned, the products to be prescribed in the following years will be those of latest generation, such as thiazolidinedione, GLP-1 analogues, DPP-4 inhibitors, as well as their fixed combinations with metformine. Rapid or slow acting Insulin analogues and their combinations with isophane insulins replace the classic insulins which seem to be outdated.

  2. Comparison Between LES and RANS Modeling of Turbulent Swirling Flows and Swirling Diffusion Combustion

    Institute of Scientific and Technical Information of China (English)

    胡瓅元; 周力行; 张健

    2005-01-01

    Turbulent swirling flows and methane-air swirling diffusion combustion are simulated by both large-eddy simulation (LES) using a Smagorinsky-Lilly subgrid-scale (SGS) turbulence model, a second-order moment (SOM) subgrid-scale combustion model and an eddy break up (EBU) combustion model and Reynolds-averaged NavierStokes (RANS) modeling using the Reynolds stress equation model and a second-order moment (SOM) combustion model. For swirling flows, the LES statistical results give better agreement with the experimental results than the RANS modeling, indicating that the adopted subgrid-scale turbulence model is suitable for swirling flows. For swirling combustion, both the proposed SOM SGS combustion model and the RANS-SOM model give the results in good agreement with the experimental results, but the LES-EBU modeling results are not in agreement with the experimental results.

  3. A decade of innovation in pharmaceutical R&D: the Chorus model.

    Science.gov (United States)

    Owens, Paul K; Raddad, Eyas; Miller, Jeffrey W; Stille, John R; Olovich, Kenneth G; Smith, Neil V; Jones, Rosie S; Scherer, Joel C

    2015-01-01

    Chorus is a small, operationally independent clinical development organization within Eli Lilly and Company that specializes in drug development from candidate selection to clinical proof of concept. The mission of Chorus is to achieve proof of concept rapidly and at a low cost while positioning successful projects for 'pharma-quality' late-stage development. Chorus uses a small internal staff of experienced drug developers and a network of external vendors to design and implement chemistry, manufacturing and control processes, preclinical toxicology and biology, and Phase I/II clinical trials. In the decade since it was established, Chorus has demonstrated substantial productivity improvements in both time and cost compared to traditional pharmaceutical research and development. Here, we describe its development philosophy, organizational structure, operational model and results to date.

  4. Incretinas, incretinomiméticos, inhibidores de DPP IV: (2ª parte Incretins, Incretinmimetics, Inhibitors (2nd part

    Directory of Open Access Journals (Sweden)

    Claudia Bayón

    2010-09-01

    Full Text Available En los últimos años se reconoce un nuevo mecanismo involucrado en la fisiopatología de la Diabetes Mellitus tipo 2: el déficit de producción y/o acción de las incretinas. Las incretinas son enterohormonas que estimulan la secreción de insulina en respuesta a la ingesta de nutrientes. Glucagon like peptide-1 (GLP1 y Polipéptido insulinotrópico glucosa dependiente (GIP son las principales incretinas descubiertas hasta hoy. Ambas presentan también efecto trófico sobre las células beta de los islotes pancreáticos. GLP-1 presenta otras acciones como son la inhibición de la secreción de glucagón, enlentecimiento del vaciamiento gástrico e inhibición del apetito. Ambas incretinas son rápidamente clivadas por la enzima dipeptidil peptidasa 4 (DPP-4. Nuevas drogas como los incretinomiméticos, análogos y los inhibidores de DPP-4 se presentan como una terapéutica prometedora para los pacientes con diabetes tipo 2. Conflicto de intereses: Dr. León Litwak - Miembro del Board Latinoamericano de Eli Lilly y Sanofi Aventis - Miembro del Board Nacional de los laboratorios Novo Nordisk, Novartis, GlaxoSmithKline, Sanofi Aventis, Boheringer Ingelheim, Bristol Myers, Astra Zeneca - Investigador principal de protocolos pertenecientes a Eli Lilly, Novo Nordisk, Novartis, GlaxoSmithKline, Takeda, PPDF, Pfizer, Merck Sharp and Dôhme, Amger, Roche, Minimed, Quintiles - Conferencista de los laboratorios mencionados.Two main pathophysiological mechanisms are currently involved in Type 2 Diabetes (T2DM, insulin resistance and impairment of beta cell function. However, in recent years a new mechanism was reported: a significant decrease in incretins production and/or action. Incretins are gastrointestinal hormones whose main action is stimulating insulin secretion in response to nutrients. The best known incretins are glucagon like peptide-1 (GLP-1 and Gastric insulinotropic peptide (GIP. GLP-1 and GIP not only increase insulin secretion, but also

  5. A coupled dynamical-radiational model of stratocumulus

    Science.gov (United States)

    Ye, Weizuo

    1990-05-01

    A model dealing with interactions between the air and low stratiform clouds is presented based on the mixed-layer model Lilly (1968) pioneered and on Deardorff's three dimensional numerical model results. Its main new aspects lie in 1) consideration of the natures of both the atmosphere and cloud; 2) a new entrainment velocity scheme with few arbitrary assumptions; 3) transition from one-mixed layer to two-mixed layer model; and 4) parameterization of radiation and precipitation calculations. The model results for radiation, moisture, and heat turbulent fluxes turn out to be in good agreement with those calculated or observed by Kawa (1988), Nicholls (1984), and Schmets et al. (1981) in California, the North Sea, and the North Atlantic, respectively. Basically, this paper furnishes the theoretical basis for a model to address questions concerning the time-evolution of thermodynamical profiles both in cloud and out of cloud. The applications of this model wil be in a separate paper.

  6. THE VITAMIN B(1) AND B(2) G CONTENT OF LIVER EXTRACT AND BREWERS' YEAST CONCENTRATE.

    Science.gov (United States)

    Miller, D K; Rhoads, C P

    1934-02-28

    1. Liver extract powder, No. 343 Lilly, and the same material prepared for parenteral use, when administered daily by mouth in amounts derived from 2.5 gm. of fresh whole liver, to rats weighing from 40 to 50 gm., contain sufficient vitamin B(1) to support normal growth, provided the animals receive in addition an adequate amount of vitamin B(2) G. Moreover, liver extract in the forms mentioned, administered in the same amounts, does not contain sufficient vitamin B(2) G to maintain normal growth of similar rate when all other necessary constituents of the diet are provided. 2. Liver extract (Lilly) in the form prepared for parenteral use, when administered daily by intraperitoneal injections, in amounts derived from 2.5 gm. of fresh whole liver, to rats under standard experimental conditions, does not contain sufficient vitamin B(2) G to maintain normal growth. Furthermore, the amount of vitamin B(1) present in liver extract in this form is not as effective in supporting normal growth when given by intraperitoneal injection as it is when given by mouth. 3. Vegex, when administered daily in amounts of 50, 150, and 250 mg. to rats of 40 to 50 gm. in weight contains sufficient vitamin B(1) to maintain normal growth of the rats, provided the animals receive in addition an adequate amount of vitamin B(2) G. However, vegex in the same amounts does not contain sufficient vitamin B(2) G to support normal growth of similar rats when all other necessary constituents of the diet are provided. 4. These experiments indicate that the extrinsic, anti-anemic factor of Castle and the thermostable growth-promoting food constituent, commonly known as vitamin B(2) G, are not identical.

  7. Evaluation of O6-methylguanine-DNA methyltransferase enzyme expression effect on survival of patients with Grade 4 brain astrocytoma

    Directory of Open Access Journals (Sweden)

    Simin Hemati

    2014-01-01

    Full Text Available Background: High-grade astrocytoma (Grade 4 or glioblastoma multiforme (GBM are deadly brain tumors. New therapies attempt to increase lifetime and quality of life in patients with malignant astrocytoma. O6-methylguanine-DNA methyltransferase (MGMT enzyme expression may be effective in prognosis and response to treatment of these patients. The aim of this study was assessment of MGMT enzyme expression in patients with astrocytoma Grade 4. Materials and Methods: In this study, 48 patients with GBM that were treated with surgery, chemotherapy and radiotherapy were investigated and followed-up for 47 months for the survival rate. Pathology blocks of patients were examined for MGMT enzyme expression using immunohistochemistry method. Results: The patients were 34 males and 14 females. The ages ranged from 24 to 77 years, with a mean age of 53.52 ± 13.39 years. There was no significant difference between two groups (positive and negative MGMT enzyme expression in overall survival (median [range] 11.5 [4-30] vs. 13 [5-22], P = 0.9. The results of our study showed that patients although who were undergone near total surgery had higher overall survival than the group of patients who had biopsy only however, it was not significant. Patients who were treated with temozolomide (TMZ (Temodal, Merck Canada had significant overall median survival (14.5 more than the patients who were treated with Procarbazine (Roche, Swiss-Lomustine (Lilly, USA-Vincristine (Lilly, USA regimen (8.75 (P < 0.05. Conclusion: O6-methylguanine-DNA methyltransferase enzyme expression had no effect on survival of patients with Grade 4 brain astrocytoma TMZ may increase survival rate.

  8. Patient involvement in clinical research: why, when, and how

    Directory of Open Access Journals (Sweden)

    Sacristán JA

    2016-04-01

    Full Text Available José A Sacristán,1 Alfonso Aguarón,2 Cristina Avendaño-Solá,3 Pilar Garrido,4 Juan Carrión,5 Alipio Gutiérrez,6 Robert Kroes,7 Angeles Flores11Medical Department, Lilly Spain, 2Myeloma Patients Europe, 3Research Ethics Committee, University Hospital Puerta de Hierro, 4Oncology Department, Hospital Ramón y Cajal, 5FEDER (Spanish Federation for Rare Diseases, 6National Association of Health Journalists, Madrid, Spain; 7Clinical Open Innovation, Lilly Europe, Amsterdam, the Netherlands Abstract: The development of a patient-centered approach to medicine is gradually allowing more patients to be involved in their own medical decisions. However, this change is not happening at the same rate in clinical research, where research generally continues to be carried out on patients, but not with patients. This work describes the why, when, and how of more active patient participation in the research process. Specific measures are proposed to improve patient involvement in 1 setting priorities, 2 study leadership and design, 3 improved access to clinical trials, 4 preparation and oversight of the information provided to participants, 5 post-study evaluation of the patient experience, and 6 the dissemination and application of results. In order to achieve these aims, the relative emphases on the ethical principles underlying research need to be changed. The current model based on the principle of beneficence must be left behind, and one that upholds the ethical principles of autonomy and non maleficence should be embraced. There is a need to improve the level of information that patients and society as a whole have on research objectives and processes; the goal is to promote the gradual emergence of the expert patient.Keywords: patients, research, clinical trials, bioethics, engagement

  9. Correlation between pain response and improvements in patient-reported outcomes and health-related quality of life in duloxetine-treated patients with diabetic peripheral neuropathic pain

    Directory of Open Access Journals (Sweden)

    Ogawa K

    2015-08-01

    Full Text Available Kei Ogawa,1 Shinji Fujikoshi,2 William Montgomery,3 Levent Alev1 1Medical Science, 2Statistical Science, Eli Lilly Japan K.K., Kobe, Japan; 3Global Patient Outcomes and Real World Evidence, Eli Lilly Australia Pty Ltd, West Ryde, NSW, Australia Objective: We assessed whether quality of life (QoL improvement in duloxetine-treated patients with diabetic peripheral neuropathic pain (DPNP correlates with the extent of pain relief.Methods: Pooled data from three multicountry, double-blind, 12-week, placebo-controlled trials of duloxetine-treated (duloxetine 60 mg once daily; total number =335 patients with DPNP were analyzed. Based on improvement in 24-hour average pain scores, patients were stratified into four groups. Improvement in QoL, which was measured as the change from baseline in two patient-reported health outcome measures (Short Form [SF]-36 and five-dimension version of the EuroQol Questionnaire [EQ-5D], was evaluated and compared among the four groups. Pearson’s correlation coefficient was calculated to assess the correlation between improvement in pain scores and improvement in QoL.Results: The group with more pain improvement generally showed greater mean change from baseline in all of the SF-36 scale scores and on the EQ-5D index. Pearson’s correlation coefficients ranged from 0.114 to 0.401 for the SF-36 scale scores (P<0.05, and it was 0.271 for the EQ-5D (P<0.001.Conclusion: Improvement in pain scores was positively correlated with improvement in QoL and patient-reported outcomes in duloxetine-treated patients. Keywords: diabetic peripheral neuropathic pain, duloxetine, efficacy, function, quality of life

  10. Development, implementation and critique of a bioethics framework for pharmaceutical sponsors of human biomedical research.

    Science.gov (United States)

    Van Campen, Luann E; Therasse, Donald G; Klopfenstein, Mitchell; Levine, Robert J

    2015-11-01

    Pharmaceutical human biomedical research is a multi-dimensional endeavor that requires collaboration among many parties, including those who sponsor, conduct, participate in, or stand to benefit from the research. Human subjects' protections have been promulgated to ensure that the benefits of such research are accomplished with respect for and minimal risk to individual research participants, and with an overall sense of fairness. Although these protections are foundational to clinical research, most ethics guidance primarily highlights the responsibilities of investigators and ethics review boards. Currently, there is no published resource that comprehensively addresses bioethical responsibilities of industry sponsors; including their responsibilities to parties who are not research participants, but are, nevertheless key stakeholders in the endeavor. To fill this void, in 2010 Eli Lilly and Company instituted a Bioethics Framework for Human Biomedical Research. This paper describes how the framework was developed and implemented and provides a critique based on four years of experience. A companion article provides the actual document used by Eli Lilly and Company to guide ethical decisions regarding all phases of human clinical trials. While many of the concepts presented in this framework are not novel, compiling them in a manner that articulates the ethical responsibilities of a sponsor is novel. By utilizing this type of bioethics framework, we have been able to develop bioethics positions on various topics, provide research ethics consultations, and integrate bioethics into the daily operations of our human biomedical research. We hope that by sharing these companion papers we will stimulate discussion within and outside the biopharmaceutical industry for the benefit of the multiple parties involved in pharmaceutical human biomedical research.

  11. Lessons from a BACE1 inhibitor trial: off-site but not off base.

    Science.gov (United States)

    Lahiri, Debomoy K; Maloney, Bryan; Long, Justin M; Greig, Nigel H

    2014-10-01

    Alzheimer's disease (AD) is characterized by formation of neuritic plaque primarily composed of a small filamentous protein called amyloid-β peptide (Aβ). The rate-limiting step in the production of Aβ is the processing of Aβ precursor protein (APP) by β-site APP-cleaving enzyme (BACE1). Hence, BACE1 activity plausibly plays a rate-limiting role in the generation of potentially toxic Aβ within brain and the development of AD, thereby making it an interesting drug target. A phase II trial of the promising LY2886721 inhibitor of BACE1 was suspended in June 2013 by Eli Lilly and Co., due to possible liver toxicity. This outcome was apparently a surprise to the study's team, particularly since BACE1 knockout mice and mice treated with the drug did not show such liver toxicity. Lilly proposed that the problem was not due to LY2886721 anti-BACE1 activity. We offer an alternative hypothesis, whereby anti-BACE1 activity may induce apparent hepatotoxicity through inhibiting BACE1's processing of β-galactoside α-2,6-sialyltransferase I (STGal6 I). In knockout mice, paralogues, such as BACE2 or cathepsin D, could partially compensate. Furthermore, the short duration of animal studies and short lifespan of study animals could mask effects that would require several decades to accumulate in humans. Inhibition of hepatic BACE1 activity in middle-aged humans would produce effects not detectable in mice. We present a testable model to explain the off-target effects of LY2886721 and highlight more broadly that so-called off-target drug effects might actually represent off-site effects that are not necessarily off-target. Consideration of this concept in forthcoming drug design, screening, and testing programs may prevent such failures in the future.

  12. Costs associated with rheumatoid arthritis in Italy: past, present, and future

    Directory of Open Access Journals (Sweden)

    Benucci M

    2016-02-01

    Full Text Available Maurizio Benucci,1 Veronica Rogai,2 Fabiola Atzeni,3 Volker Hammen,4 Piercarlo Sarzti-Puttini,3 Alberto Migliore5 1Rheumatology Unit, S.Giovanni di Dio Hospital, Florence, Italy; 2Eli Lilly Italia SpA, Sesto Fiorentino, Italy; 3Rheumatology Unit, L Sacco Hospital, Milan, Italy; 4Lilly Deutschland GmbH, Bad Homburg, Germany; 5Villa San Pietro Fatebenefratelli Hospital, Rome, Italy Abstract: This literature review examines available evidence on the current and past costs associated with rheumatoid arthritis (RA in Italy, together with the future health-economic prospects for the disease. Studies have been conducted to date on the prevalence, or the associated costs, of RA in Italy. Although future changes in the incidence of RA are a matter of debate, the impact of RA on health care costs is expected to grow in coming decades in line with projected increases in life expectancy and in the proportion of elderly people in Italy. It has been estimated that the indirect (productivity loss and informal care and intangible (deterioration in health-related quality of life costs of the disease will contribute to an increase in national health service expenditure, which will correspond to 1% of the total health care costs of the nation in the near future. The introduction of biological agents for the treatment of rheumatic diseases has resulted in an increase in the direct costs of RA; however, economic analyses that exclude indirect costs will underestimate the full economic impact of RA. The effectiveness of innovative therapies in preventing disease progression and functional impairment may, over time, attenuate the cost impact of RA in terms of hospitalizations and work absenteeism. Further research is needed to develop estimates of the economic impact of different therapeutic approaches in patients with RA in Italy, in order to provide tools that can drive the choice of the most cost-effective therapeutic option while maintaining high-quality care

  13. Frontiers in Numerical Relativity

    Science.gov (United States)

    Evans, Charles R.; Finn, Lee S.; Hobill, David W.

    2011-06-01

    Christopher S. Kochanek and Charles R. Evans; 22. Relativistic hydrodynamics James R. Wilson and Grant J. Mathews; 23. Computational dynamics of U(1) gauge strings: probability of reconnection of cosmic strings Richard A. Matzner; 24. Dynamically inhomogenous cosmic nucleosynthesis Hannu Kurki-Suonio; 25. Initial value solutions in planar cosmologies Peter Anninos, Joan Centrella and Richard Matzner; 26. An algorithmic overview of an Einstein solver Roger Ove; 27. A PDE compiler for full-metric numerical relativity Jonathan Thornburg; 28. Numerical evolution on null cones R. Gomez and J. Winicour; 29. Normal modes coupled to gravitational waves in a relativistic star Yasufumi Kojima; 30. Cosmic censorship and numerical relativity Dalia S. Goldwirth, Amos Ori and Tsvi Piran.

  14. Efficacy comparison of duloxetine and SSRIs at doses approved in Japan

    Directory of Open Access Journals (Sweden)

    Harada E

    2015-01-01

    Full Text Available Eiji Harada,1 Alexander Schacht,2 Tsukasa Koyama,3 Lauren Marangell,4,5 Toshinaga Tsuji,6 Rodrigo Escobar41Medical Science, Eli Lilly Japan K.K, Kobe, Japan; 2Global Statistical Sciences, Eli Lilly and Company, Bad Homburg, Germany; 3Clinical Research Center, Ohyachi Hospital, Sapporo, Japan; 4Eli Lilly and Company, Indianapolis, IN, 5The University of Texas Health Science Center, Houston, TX, USA; 6Medical Affairs, Shionogi & Co Ltd, Osaka, JapanBackground: Approved doses of antidepressants in Japan are usually lower than those in the USA and European Union, but to date meta-analyses comparing antidepressants have all used the higher doses approved in the USA and European Union and often have used indirect comparisons. The purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors (SSRIs at the doses approved in Japan.Methods: Pooled data were analyzed from four randomized, double-blind, placebo-controlled studies that compared duloxetine at the dose range approved in Japan (40–60 mg/day with other SSRIs (paroxetine 20 mg/day or escitalopram 10 mg/day and placebo in patients with major depressive disorder. In total, 1,694 patients were included in the analysis (duloxetine, n=688; selective serotonin reuptake inhibitors, n=690; placebo, n=316. The primary outcome measure was the mean change from baseline at week 8 in 17-item Hamilton Rating Scale for Depression (HAMD17 total and subscale scores.Results: Duloxetine and both selective serotonin reuptake inhibitors were superior to placebo in HAMD17 total score at week 8 in both the all-randomized group and the more severe subgroup (HAMD17 total scores ≥19. Duloxetine was superior to SSRIs in improving the HAMD17 Retardation subscale score (least squares mean difference [95% confidence interval]: all-randomized group, −0.33 [−0.60, −0.07], P=0.015; severe subgroup,

  15. Prevalence and Cost of Subsequent Fractures Among U.S. Patients with an Incident Fracture.

    Science.gov (United States)

    Weaver, Jessica; Sajjan, Shiva; Lewiecki, E Michael; Harris, Steven T; Marvos, Panagiotis

    2017-04-01

    of patients with a subsequent fracture paralleled those observed in the Medicare group: 24.5% (n = 808) in patients with multiple index fractures, 22.0% (n = 525) in those with hip fracture, and 14.5% (n = 841) in those with vertebral fracture. For vertebral, hip, and nonhip nonvertebral fractures, subsequent fractures were most frequently of the same type as the index fracture. The mean total health care cost (sum of medical and pharmacy costs) in the year following the incident fracture for the Medicare group was $27,844 and differed significantly between patients with and without a subsequent fracture ($34,897 vs. $20,790; P commercial group was $29,316 and also differed significantly between patients with and without a subsequent fracture ($39,501 vs. $19,131; P company at the time of the study. Lewiecki has received consulting and/or speaker honoraria from Merck, AbbVie, AgNovos Healthcare, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Radius Health, Shire, and TheraNova. Lewiecki has received research grant support from Merck, Amgen, and Eli Lilly and Company and serves as a board member for the National Osteoporosis Foundation, the International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico. Harris has received consulting honoraria from Merck, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Gilead Sciences, Primus Pharmaceuticals, and Radius Health. Study concept and design were contributed by Weave and Sajjan. Lewiecki collected the data, and data interpretation was performed by all the authors. The manuscript was written and revised by Weaver, Lewiecki, and Harris.

  16. Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

    Directory of Open Access Journals (Sweden)

    Ascher-Svanum H

    2014-06-01

    Full Text Available Haya Ascher-Svanum,1 Diego Novick,2,3 Josep Maria Haro,4 Jordan Bertsch,4 David McDonnell,1 Holland Detke11Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, Surrey, UK; 3Departament de Psiquiatria, Universitat Autonoma de Barcelona, Spain; 4Parc Sanitari Sant Joan de Déu, Centro de Investigación Biomédica en Red en el Área de Salud Mental, Universitat de Barcelona, Barcelona, SpainBackground: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI, and whether observed changes differ from those seen with oral olanzapine.Methods: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264 with daily oral olanzapine (10 mg/day; n=260. Levels of functioning were assessed with the Heinrichs–Carpenter Quality of Life Scale. Functional status was also classified as “good”, “moderate”, or “poor”, using a previous data-driven approach. Changes in functional levels were assessed with McNemar’s test and comparisons between olanzapine-LAI and oral olanzapine employed the Student’s t-test. Results: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score from 64.0–70.8 (P<0.001. Patients on oral ­olanzapine also increased their level of functioning from 62.1–70.1 (P<0.001. At baseline, 19.2% of the olanzapine-LAI-treated patients had a “good” level of functioning, which increased to 27.5% (P<0.05. The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001. Results did not significantly differ between

  17. Adherence and persistence with branded antidepressants and generic SSRIs among managed care patients with major depressive disorder

    Directory of Open Access Journals (Sweden)

    Xianchen Liu

    2011-03-01

    Full Text Available Xianchen Liu1,2, Yi Chen3, Douglas E Faries31Former employee, Eli Lilly and Company, Indianapolis, Indiana, USA; 2Indiana University Department of Psychiatry, Indianapolis, Indiana, USA; 3Eli Lilly and Company, Indianapolis, Indiana, USAObjective: This study compared adherence and persistence of three branded antidepressants: the serotonin and norepinephrine reuptake inhibitors (SNRIs duloxetine and venlafaxine XR, and the selective serotonin reuptake inhibitor (SSRI escitalopram; and generic selective SSRIs, and examined demographic and clinical predictors of adherence and persistence in patients with major depressive disorder in usual care settings.Method: A total of 44,026 patients (18 to 64 years from a large commercial administrative claims database were classified as initiators of duloxetine (n = 7,567, venlafaxine XR (n = 6,106, escitalopram (n = 10,239, or generic SSRIs (n = 20,114 during 2006. Adherence was defined as the medication possession ratio of ≥ 0.8 and persistence as the length of therapy without exceeding a 15-day gap. Pairwise comparisons from multivariate logistic regression and Cox proportional hazards models were performed to examine predictors of adherence and persistence.Results: Adherence rate after one year was significantly higher in duloxetine recipients (38.1% than patients treated with venlafaxine XR (34.0%, escitalopram (25.4%, or generic SSRIs (25.5% (all P < 0.01. Duloxetine recipients stayed on medication longer (158.5 days than those receiving venlafaxine XR (149.6 days, escitalopram (129.1 days, or generic SSRIs (130.2 days (all P < 0.001. Compared with patients treated with escitalopram or generic SSRIs, venlafaxine XR recipients had better adherence and longer persistence (P < 0.001. In addition, being aged 36 years or more, hypersomnia, anxiety disorders, and prior use of antidepressants were associated with increased adherence and persistence, while the opposite was true for comorbid chronic pain

  18. Linagliptin: a novel methylxanthin based approved dipeptidyl peptidase-4 inhibitor.

    Science.gov (United States)

    Agrawal, Ritesh; Jain, Pratima; Dikshit, S N

    2012-06-01

    Chemically, methylxanthine nucleus based Linagliptin (BI-1356, BI-1356-BS) is a dipeptidyl peptidase-IV inhibitor, which has been developed by Boehringer Ingelheim in association with Lilly for the treatment of Type-II Diabetes. Linagliptin was marketed by Lilly under the trade name Tradjenta and Trajenta. Linagliptin was approved as the once-daily dose by USFDA on 2 May 2011, for the treatment of Type-II Diabetes. Linagliptin 5mg once daily dose was approved based on a clinical trial program, which was conducted on approximately 4,000 adults with Type-II Diabetes. Linagliptin demonstrated statistically significant mean difference in HbA1c from placebo of up to 0.72 percent, when it was used monotherapically. In patients, who were not adequately controlled on metformin or metformin plus sulphonylurea, the addition of Linagliptin resulted in a statistically significant mean difference in HbA1c from placebo of -0.6 percent. Linagliptin was observed to produce significant reduction in fasting plasma glucose (FPG) compared to placebo, when used as a monotherapy in combination with metformin, sulfonylurea and/or pioglitazone. Linagliptin demonstrated significant reduction post-prandial glucose (PPG) levels in two hours as compared with placebo in monotherapy as well as in combination with metformin. In vitro assays also anticipated that Linagliptin is a potent DPPIV inhibitor as well as it exhibits good selectivity for DPP-IV as compared with other DPPs. The in-vivo studies also demonstrated same anticipation with respect to Linagliptin. Consequently, increasing the GLP-1 levels so far improved glucose tolerance in both healthy animals. X-ray crystallography anticipates that Linagliptin complexes with human DPPIV enzyme, e.g. butynyl substituent occupies the S1 hydrophobic pocket of the enzyme; the aminopiperidine substituent in the xanthine scaffold occupies the S2 subsite and its primary amine interacts with the key amino acid residues, which involves in the

  19. 6th Annual European Antibody Congress 2010: November 29-December 1, 2010, Geneva, Switzerland.

    Science.gov (United States)

    Beck, Alain; Wurch, Thierry; Reichert, Janice M

    2011-01-01

    The 6th European Antibody Congress (EAC), organized by Terrapinn Ltd., was held in Geneva, Switzerland, which was also the location of the 4th and 5th EAC. As was the case in 2008 and 2009, the EAC was again the largest antibody congress held in Europe, drawing nearly 250 delegates in 2010. Numerous pharmaceutical and biopharmaceutical companies active in the field of therapeutic antibody development were represented, as were start-up and academic organizations and representatives from the US Food and Drug Administration FDA. The global trends in antibody research and development were discussed, including success stories of recent marketing authorizations of golimumab (Simponi®) and canakinumab (Ilaris®) by Johnson & Johnson and Novartis, respectively, updates on antibodies in late clinical development (obinutuzumab/GA101, farletuzumab/MORAb-003 and itolizumab/T1 h, by Glycart/Roche, Morphotek and Biocon, respectively) and success rates for this fast-expanding class of therapeutics (Tufts Center for the Study of Drug Development). Case studies covering clinical progress of girentuximab (Wilex), evaluation of panobacumab (Kenta Biotech), characterization of therapeutic antibody candidates by protein microarrays (Protagen), antibody-drug conjugates (sanofi-aventis, ImmunoGen, Seattle Genetics, Wyeth/Pfizer), radio-immunoconjugates (Bayer Schering Pharma, Université de Nantes) and new scaffolds (Ablynx, AdAlta, Domantis/GlaxoSmithKline, Fresenius, Molecular Partners, Pieris, Scil Proteins, Pfizer, University of Zurich) were presented. Major antibody structural improvements were showcased, including the latest selection engineering of the best isotypes (Abbott, Pfizer, Pierre Fabre), hinge domain (Pierre Fabre), dual antibodies (Abbott), IgG-like bispecific antibodies (Biogen Idec), antibody epitope mapping case studies (Eli Lilly), insights in FcγRII receptor (University of Cambridge), as well as novel tools for antibody fragmentation (Genovis). Improvements of

  20. 6th Annual European Antibody Congress 2010

    Science.gov (United States)

    2011-01-01

    The 6th European Antibody Congress (EAC), organized by Terrapinn Ltd., was held in Geneva, Switzerland, which was also the location of the 4th and 5th EAC.1,2 As was the case in 2008 and 2009, the EAC was again the largest antibody congress held in Europe, drawing nearly 250 delegates in 2010. Numerous pharmaceutical and biopharmaceutical companies active in the field of therapeutic antibody development were represented, as were start-up and academic organizations and representatives from the US Food and Drug Administration (FDA). The global trends in antibody research and development were discussed, including success stories of recent marketing authorizations of golimumab (Simponi®) and canakinumab (Ilaris®) by Johnson & Johnson and Novartis, respectively, updates on antibodies in late clinical development (obinutuzumab/GA101, farletuzumab/MORAb-003 and itolizumab/T1 h, by Glycart/Roche, Morphotek and Biocon, respectively) and success rates for this fast-expanding class of therapeutics (Tufts Center for the Study of Drug Development). Case studies covering clinical progress of girentuximab (Wilex), evaluation of panobacumab (Kenta Biotech), characterization of therapeutic antibody candidates by protein microarrays (Protagen), antibody-drug conjugates (sanofi-aventis, ImmunoGen, Seattle Genetics, Wyeth/Pfizer), radio-immunoconjugates (Bayer Schering Pharma, Université de Nantes) and new scaffolds (Ablynx, AdAlta, Domantis/GlaxoSmithKline, Fresenius, Molecular Partners, Pieris, Scil Proteins, Pfizer, University of Zurich) were presented. Major antibody structural improvements were showcased, including the latest selection engineering of the best isotypes (Abbott, Pfizer, Pierre Fabre), hinge domain (Pierre Fabre), dual antibodies (Abbott), IgG-like bispecific antibodies (Biogen Idec), antibody epitope mapping case studies (Eli Lilly), insights in FcγRII receptor (University of Cambridge), as well as novel tools for antibody fragmentation (Genovis). Improvements

  1. Changes in nitrate concentrations in Scottish catchments - investigating the influence of climate and land use drivers by simulation with NIRAMS II

    Science.gov (United States)

    Pohle, Ina; Glendell, Miriam; Gair, Jonathan; Sample, James E.

    2017-04-01

    climate and land use changes on nitrate concentrations. References: Dunn, S. M., Vinten, A. J. A., Lilly, A., DeGroote, J., Sutton, M. A., and McGechan, M.: Nitrogen risk assessment model for Scotland: I. Nitrogen leaching, Hydrology and Earth System Sciences, 8, 191.204, doi:10.5194/hess-8-191-2004, 2004a. Dunn, S. M., Lilly, A., DeGroote, J., and Vinten, A. A.: Nitrogen risk assessment model for Scotland: II. Hydrological transport and model testing, Hydrology and Earth System Sciences, 8, 205.219, doi:10.5194/hess-8-205-2004, 2004b. Sample, J. E., Dunn, S. M. 2013. The effects of land use change and weather variability on surface water nitrate. Interdisciplinary conference on land use and water quality. The Hague, Netherlands, 10th to 13th June, 2013.

  2. Factors Associated with Adherence to and Treatment Duration of Erlotinib Among Patients with Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hess, Lisa M; Louder, Anthony; Winfree, Katherine; Zhu, Yajun E; Oton, Ana B; Nair, Radhika

    2017-06-01

    In lung cancer, there is an increasing number of oral agents available for patients; however, little is known about the factors associated with adherence to and treatment duration on oral medications in non-small cell lung cancer (NSCLC). To evaluate the clinical and demographic factors associated with adherence and treatment discontinuation, respectively, to oral oncolytics among patients with NSCLC. A retrospective, claims-based analysis of the Humana Research Database supplemented with medical chart review was conducted among patients with NSCLC who started an oral oncolytic between January 1, 2008, and June 30, 2013. Patients were required to be enrolled at least 1 year before the start of oral oncolytics and have no evidence of any oral oncolytic use during this period. Logistic regression models and Cox proportional hazard models were used to identify predictors associated with medication adherence and treatment duration, respectively. Among all oral oncolytics, only the cohort starting on erlotinib had sufficient sample size (n = 1,452). A wide variety of factors were found to be associated with adherence. Low-income subsidy status, previous use of intravenous chemotherapy, and lower total baseline health care costs were significantly related to decreasing adherence (each P patient out-of-pocket cost was associated with decreasing adherence to erlotinib (P patient outcomes that may be associated with low adherence to or shorter treatment duration on oral chemotherapy. This study was supported by funding from Eli Lilly and Company to Comprehensive Health Insights, a Humana company, as a collaborative research project involving employees of both companies. Hess, Winfree, Zhu, and Oton are employees of Eli Lilly and Company. Louder and Nair are employees of Comprehensive Health Insights, which received funding to complete this research. Study concept and design were contributed by Hess, Zhu, Winfree, and Oton. Nair and Louder collected the data, and data

  3. Incidence and impact of pain conditions and comorbid illnesses

    Directory of Open Access Journals (Sweden)

    Davis JA

    2011-10-01

    Full Text Available Jessica A Davis, Rebecca L Robinson, Trong Kim Le, Jin XieLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USABackground: Individuals with pain often present with more than one painful condition. The purpose of this study was to characterize the rates of comorbidity, pain medication use, and health care costs for 23 selected pain conditions in a large health plan using administrative claims data from 2005 to 2007.Methods: Eligible patients included 1,211,483 adults with at least one pain condition during the one-year study period. Pain condition cohorts were classified based on the first diagnosis present in the claims during the study period.Results: Musculoskeletal pain conditions were among the most prevalent cohorts including low back pain, osteoarthritis, and fibromyalgia. Cancer pain was the least prevalent cohort. Conditions with the lowest illness severity included migraine and painful bladder syndrome cohorts, while cohorts with diabetic neuropathy, human immunodeficiency virus (HIV-associated pain, and cancer pain were the most severe. Across cohorts, the mean number of comorbid pain conditions ranged from 1.39 (for cancer pain and migraine to 2.65 (for multiple sclerosis pain. High rates of mental health conditions were found in cohorts with HIV-associated pain and multiple sclerosis pain (42.59% and 34.78% and were lowest among cohorts with rheumatoid arthritis and psoriatic arthropathy (12.73% and 13.31%, respectively. Rates of sleep disorders ranged from 5.47% (for painful bladder syndrome to 11.59% (for multiple sclerosis pain. Overall, patients averaged 3.53 unique pain medications during the study period. Considerable annual total health care costs were observed in the cancer pain cohort and the lowest costs were observed in the postherpetic neuropathy, surgically-induced pain, migraine, and irritable bowel syndrome cohorts. Costs attributed to pain were highest among the multiple sclerosis, HIV, and cancer

  4. Safety of daily teriparatide treatment: a post hoc analysis of a Phase III study to investigate the possible association of teriparatide treatment with calcium homeostasis in patients with serum procollagen type I N-terminal propeptide elevation

    Directory of Open Access Journals (Sweden)

    Yamamoto T

    2015-07-01

    Full Text Available Takanori Yamamoto,1 Mika Tsujimoto,2 Hideaki Sowa11Medical Science, Lilly Research Laboratories, Medicines Development Unit Japan, 2Asia Pacific Statistical Science-Japan, Science and Regulatory Affairs, LRL MDU-Japan, Eli Lilly Japan K.K, Kobe, Hyogo, JapanObjective: Serum procollagen type I N-terminal propeptide (PINP, a representative marker of bone anabolic action, is strongly related to bone mineral density during teriparatide therapy. This post hoc study analyzed data from a Phase III study (ClinicalTrials.gov identifier NCT00433160 to determine if there was an association between serum PINP elevation and serum calcium concentration or calcium metabolism-related disorders.Research design and methods: Japanese subjects with osteoporosis at high risk of fracture were randomized 2:1 to teriparatide 20 µg/day (n=137 or placebo (n=70 for a 12-month double-blind treatment period, followed by 12 months of open-label teriparatide treatment of all subjects.Main outcome measures: Serum PINP levels were measured at baseline, and after 1, 3, 6, 12, 18, and 24 months of treatment. Serum calcium levels were measured at baseline, and after 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of treatment.Results: Serum PINP increased from baseline to 1 month of treatment and then remained high through 24 months. Twenty-eight of 195 subjects experienced PINP elevations >200 µg/L during teriparatide treatment. Serum calcium concentration in both the teriparatide and placebo groups remained within the normal range. There was no clinically relevant difference in serum calcium concentration between subjects with PINP >200 µg/L and subjects with PINP ≤200 µg/L. Two subjects experienced hypercalcemia and recovered without altering teriparatide treatment. Adverse events possibly related to calcium metabolism disorders included periarthritis calcarea (one subject and chondrocalcinosis pyrophosphate (two subjects, but neither was accompanied with a significant increase

  5. Evaluating preferences for profiles of glucagon-like peptide-1 receptor agonists among injection-naive type 2 diabetes patients in Japan

    Directory of Open Access Journals (Sweden)

    Gelhorn HL

    2016-07-01

    Full Text Available Heather L Gelhorn,1 Elizabeth D Bacci,2 Jiat Ling Poon,1 Kristina S Boye,3 Shuichi Suzuki,4 Steven M Babineaux3 1Outcomes Research, Evidera, Bethesda, MD, 2Evidera, Seattle, WA, 3Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 4Medicines Development Unit Japan, Eli Lilly Japan, Kobe, Japan Objective: The objective of this study was to use a discrete choice experiment (DCE to estimate patients’ preferences for the treatment features, safety, and efficacy of two specific glucagon-like peptide-1 receptor agonists, dulaglutide and liraglutide, among patients with type 2 diabetes mellitus (T2DM in Japan.Methods: In Japan, patients with self-reported T2DM and naive to treatment with self-injectable medications were administered a DCE through an in-person interview. The DCE examined the following six attributes of T2DM treatment, each described by two levels: “dosing frequency”, “hemoglobin A1c change”, “weight change”, “type of delivery system”, “frequency of nausea”, and “frequency of hypoglycemia”. Part-worth utilities were estimated using logit models and were used to calculate the relative importance (RI of each attribute. A chi-square test was used to determine the differences in preferences for the dulaglutide versus liraglutide profiles.Results: The final evaluable sample consisted of 182 participants (mean age: 58.9 [standard deviation =10.0] years; 64.3% male; mean body mass index: 26.1 [standard deviation =5.0] kg/m2. The RI values for the attributes in rank order were dosing frequency (44.1%, type of delivery system (26.3%, frequency of nausea (15.1%, frequency of hypoglycemia (7.4%, weight change (6.2%, and hemoglobin A1c change (1.0%. Significantly more participants preferred the dulaglutide profile (94.5% compared to the liraglutide profile (5.5%; P<0.0001.Conclusion: This study elicited the preferences of Japanese T2DM patients for attributes and levels

  6. Optimizing weight control in diabetes: antidiabetic drug selection

    Directory of Open Access Journals (Sweden)

    S Kalra

    2010-08-01

    Full Text Available S Kalra1, B Kalra1, AG Unnikrishnan2, N Agrawal3, S Kumar41Bharti Hospital, Karnal; 2Amrita Institute of Medical Science, Kochi; 3Medical College, Gwalior; 4Excel Life Sciences, Noida, IndiaDate of preparation: 18th August 2010Conflict of interest: SK has received speaker fees from Novo Nordisk, sanofi-aventis, MSD, Eli Lilly, BMS, and AstraZeneca.Clinical question: Which antidiabetic drugs provide optimal weight control in patients with type 2 diabetes?Results: Metformin reduces weight gain, and may cause weight loss, when given alone or in combination with other drugs. Pioglitazone and rosiglitazone use is associated with weight gain. Use of the glucagon-like peptide-1 (GLP-1 analogs, liraglutide and exenatide, is associated with weight loss. Dipeptidyl peptidase-4 (DPP-4 inhibitors are considered weight-neutral. Results with insulin therapy are conflicting. Insulin detemir provides weight control along with glycemic control.Implementation: • Weight gain is considered an inevitable part of good glycemic control using conventional modalities of treatment such as sulfonylureas.• Use of metformin, weight-sparing insulin analogs such as insulin detemir, and liraglutide, should be encouraged as monotherapy, or in combination with other drugs.Keywords: weight control, diabetes

  7. Circulation of core collection monographs in an academic medical library.

    Science.gov (United States)

    Schmidt, C M; Eckerman, N L

    2001-04-01

    Academic medical librarians responsible for monograph acquisition face a challenging task. From the plethora of medical monographs published each year, academic medical librarians must select those most useful to their patrons. Unfortunately, none of the selection tools available to medical librarians are specifically intended to assist academic librarians with medical monograph selection. The few short core collection lists that are available are intended for use in the small hospital or internal medicine department library. As these are the only selection tools available, however, many academic medical librarians spend considerable time reviewing these collection lists and place heavy emphasis on the acquisition of listed books. The study reported here was initiated to determine whether the circulation of listed books in an academic library justified the emphasis placed on the acquisition of these books. Circulation statistics for "listed" and "nonlisted" books in the hematology (WH) section of Indiana University School of Medicine's Ruth Lilly Medical Library were studied. The average circulation figures for listed books were nearly two times as high as the corresponding figures for the WH books in general. These data support the policies of those academic medical libraries that place a high priority on collection of listed books.

  8. The Order of the Dolphin: Origins of SETI

    Science.gov (United States)

    Temming, Maria; Crider, Anthony

    2016-01-01

    In 1961, the National Academy of Sciences organized a meeting on the search for extraterrestrial intelligence (SETI) at the National Radio Astronomy Observatory in Green Bank, West Virginia. The ten scientists who attended, including future SETI icons such as Frank Drake and Carl Sagan, represented a variety of scientific fields. At the conclusion of the meeting, the attendees adopted the moniker "The Order of the Dolphin," in honor of participant John Lilly's work on interspecies communication. Since this seminal meeting, researchers in each of the attendees' fields have contributed in some way to the search for intelligent life. This study investigates the circumstances that led to each attendee's invitation to Green Bank and explores SETI as the legacy of this meeting. We will focus in this talk on the SETI connections of two attendees, astronomer Otto Struve and physicist Philip Morrison, both in regards to their personal contributions to SETI and the influence of their work on subsequent SETI research. Specifically, we will examine proposals by Otto Struve for exoplanet discovery methods, and Philip Morrison for radio searches that laid the groundwork for modern SETI.

  9. VizieR Online Data Catalog: COSMOS photometric redshift catalog (Ilbert+, 2009)

    Science.gov (United States)

    Ilbert, O.; Capak, P.; Salvato, M.; Aussel, H.; McCracken, H. J.; Sanders, D. B.; Scoville, N.; Kartaltepe, J.; Arnouts, S.; Le Floc'h, E.; Mobasher, B.; Taniguchi, Y.; Lamareille, F.; Leauthaud, A.; Sasaki, S.; Thompson, D.; Zamojski, M.; Zamorani, G.; Bardelli, S.; Bolzonella, M.; Bongiorno, A.; Brusa, M.; Caputi, K. I.; Carollo, C. M.; Contini, T.; Cook, R.; Coppa, G.; Cucciati, O.; de la Torre, S.; de Ravel, L.; Franzetti, P.; Garilli, B.; Hasinger, G.; Iovino, A.; Kampczyk, P.; Kneib, J.-P.; Knobel, C.; Kovac, K.; Le Borgne, J. F.; Le Brun, V.; Fevre, O. L.; Lilly, S.; Looper, D.; Maier, C.; Mainieri, V.; Mellier, Y.; Mignoli, M.; Murayama, T.; Pello, R.; Peng, Y.; Perez-Montero, E.; Renzini, A.; Ricciardelli, E.; Schiminovich, D.; Scodeggio, M.; Shioya, Y.; Silverman, J.; Surace, J.; Tanaka, M.; Tasca, L.; Tresse, L.; Vergani, D.; Zucca, E.

    2017-03-01

    Compared with the previous optical/NIR catalog (Capak et al., 2007ApJS..172...99C, Cat. II/284), the new photometry implements 14 new medium/narrowband data from the Subaru Telescope, deep ground-based NIR data (J and K bands), and Spitzer-IRAC data. The spectroscopic sample used to calibrate/test the photo-z is 10 times larger at i+AB1.5. Hereafter, we detail the photometric and spectroscopic data used to measure the photo-z. Fluxes are measured in 30 bands from data taken on the Subaru (4200-9000Åg), CFHT (3900-21500Å), UKIRT (12500Å), Spitzer (3.6-8um), and GALEX (1500.2300Å) telescopes. We refer to P. Capak et al. (2008, in preparation) for a complete description of the observations, data reduction, and the photometry catalog. Photometric catalogue from P. Capak Photo-z catalogue from O. Ilbert PIs of the photometric data: D.B. Sanders, N. Scoville, Y. Tanigushi Data reducers: H. Aussel, P. Capak, H. McCracken, M. Salvato, S. Sasaki,D. Thompson, O. Ilbert, J. Kartaltepe, E. Le Floc'h, D. Looper, D.B. Sanders, N. Scoville Spectroscopic redshifts for validation from the zCOSMOS team (PI S. Lilly), from J. Kartaltepe and from P. Capak Identification of the Xray sources in the optical catalogue M. Brusa, G. Hasinger and the COSMOS/XMM team. (1 data file).

  10. Influence of fluorides upon vegetation. Preliminary tests in gardon uses

    Energy Technology Data Exchange (ETDEWEB)

    Gautier, A.; Clausmann,, P.

    1919-01-01

    Pulverized birchwood charcoal extracted with hot acids and washed in boiling water gave a soil medium containing 1.87 mg F per kg. The soil was composed of purified charcoal, 1000 g; Al/sub 2/O/sub 3/ as a jelly, 120 g; CaCO/sub 3/, 730 g (F = 0.002), humus, 27.3 g; very fertile garden soil, 66.0 (F = 0.007); CaHPO/sub 4/, 24 g; KNO/sub 3/, 34 g; (NH/sub 4/)/sub 2/ SO/sub 4/, 30 g; NaCl, 3.0 g; MgCO/sub 3/, 68 g; MnCl/sub 2/, 0.80 g, ZnCO/sub 3/, 0.07; SiO/sub 2/ as jelly, 17.0; FeSO/sub 4/, 180.0; NaAsO/sub 4/, 1.4 g. This entire mixture contained 11 mg F per kg. Plants were grown in three four-liter pots, A, B, C. The pots contained the above mixture, one with charcoal, another with KF. Pot C contained good garden soil for control. The effects of F were estimated by measuring the height of the plant and when the seed was produced, the weight of the seed. Fluorine exerted a favorable influence upon Gressin alenois, cabbage; Spergula arvensis, Escholtzia California, spinach, yellow day-lilly, viperine, Oignon communis and hemp. An unfavorable influence was observed with dwarf peas and sweet peas.

  11. Morphologies of ~190,000 Galaxies at z=0-10 Revealed with HST Legacy Data II. Evolution of Clumpy Galaxies

    CERN Document Server

    Shibuya, Takatoshi; Kubo, Mariko; Harikane, Yuichi

    2015-01-01

    We investigate evolution of clumpy galaxies with the Hubble Space Telescope (HST) samples of ~190,000 photo-z and Lyman break galaxies at z~0-8. We detect clumpy galaxies with off-center clumps in a self-consistent algorithm that is well tested with previous study results, and measure the number fraction of clumpy galaxies at the rest-frame UV, f_clumpy^UV. We identify an evolutionary trend of f_clumpy^UV over z~0-8 for the first time: f_clumpy^UV increases from z~8 to z~1-3 and subsequently decreases from z~1 to z~0, which follows the trend of Madau-Lilly plot. A low average Sersic index of n~1 is found in the underlining components of our clumpy galaxies at z~0-2, indicating that typical clumpy galaxies have disk-like surface brightness profiles. Our f_clumpy^UV values correlate with physical quantities related to star formation activities for star-forming galaxies at z~0-7. We find that clump colors tend to be red at a small galactocentric distance for massive galaxies with log(M_*/M_sun)>~11. All of these...

  12. Relationship of sleep, respiration, and anesthesia in the porpoise: a preliminary report.

    Science.gov (United States)

    McCormick, J G

    1969-03-01

    The porpoise, an air-breathing mammal whose habits are entirely aquatic, presents special problems of respiration, sleep, and anesthesia. These problems have been studied in three species, Tursiops truncatus, Lagenorhynchus obliquidens, and Phocoenoides dalli. The respiratory rhythm is unusual in that there is an extended pause-an apneustic plateau-between periods of expiration and inspiration. This rhythm has been observed under waking conditions, during sleep, and also when the animal is anesthetized. Two kinds of sleep behavior have been identified in Tursiops and Lagenorhynchus. In one of these, which is a light phase, the animal rests on the tank bottom for short periods, up to perhaps four minutes, and then comes to the surface to breathe. In a deeper phase the animal maintains itself at the surface for extended periods, breathing in an automatic fashion. In Phocoenoides no sleep behavior has been observed at any time.I have examined the special theory of Dr. John C. Lilly regarding respiration and sleep in the porpoise, which is based upon the assumption that respiration in this animal is altogether voluntary, and from my observations have concluded that respiration in the porpoise can be automatic or can be brought under voluntary control, just as in other mammals. Also the anesthetization of this animal can be carried out safely by methods that correspond closely to those employed in other animals.

  13. Keystone Symposium on Antibodies as Drugs: March 27-April 1, 2009, Whistler, BC CA.

    Science.gov (United States)

    Wurch, Thierry; Larbouret, Christel; Robert, Bruno

    2009-01-01

    The symposium on Antibodies as Drugs, organized by Keystone Symposia and chaired by J. Marks, (University of California Los Angeles, USA), E.S. Ward (University of Texas Southwestern Medical Center, USA) and L. Weiner (Georgetown University Medical Center, USA), was held in Whistler, British Columbia. This Canadian Rockies village, which will host the 2010 Olympic Games, served as an enchanting backdrop to the meeting. The more than 350 speakers and attendees included scientists from major pharmaceutical firms, e.g., Abbott, MedImmune/Astra Zeneca, Bristol-Myers Squibb, Merck & Co., Pfizer, Sanofi-Aventis, Schering, GlaxoSmithKline, Eli Lilly, Hoffmann LaRoche, Novartis, Wyeth, and biotechnology companies, e.g., Ablynx, Medarex, Morphosys, GenMab, Amgen, Genentech, ImmunoGen, Agensys, Domantis, Biogen Idec, Centocor, LFB, Micromet, PDL Biopharma, Borean Pharma, Dyax Corp., Symphogen and Syntonix. Academic research groups at Imperial College London, University of Oxford, ETH Zürich, Scripps, Institute Cochin, Karolinska Institute, Utrecht University, Harvard Medical School, Massachusetts Institute of Technology, Baylor College, Paul Ehrlich Institute, University of California San Francisco, University of California San Diego, University of Nantes, University of Tours and Ludwig Institute were also represented, as were regulatory authorities, including the US Food and Drug Administration, National Institutes of Health and the Public Health Agency of Canada). The meeting was very interactive and included thoughtful exchanges during the different sessions and networking events.

  14. Large eddy simulation of mechanical mixing in anaerobic digesters.

    Science.gov (United States)

    Wu, Binxin

    2012-03-01

    A comprehensive study of anaerobic digestion requires an advanced turbulence model technique to accurately predict mixing flow patterns because the digestion process that involves mass transfer between anaerobes and their substrates is primarily dependent on detailed information about the fine structure of turbulence in the digesters. This study presents a large eddy simulation (LES) of mechanical agitation of non-Newtonian fluids in anaerobic digesters, in which the sliding mesh method is used to characterize the impeller rotation. The three subgrid scale (SGS) models investigated are: (i) Smagorinsky-Lilly model, (ii) wall-adapting local eddy-viscosity model, and (iii) kinetic energy transport (KET) model. The simulation results show that the three SGS models produce very similar flow fields. A comparison of the simulated and measured axial velocities indicates that the LES profile shapes are in general agreement with the experimental data but they differ markedly in velocity magnitudes. A check of impeller power and flow numbers demonstrates that all the SGS models give excellent predictions, with the KET model performing the best. Moreover, the performance of six Reynolds-averaged Navier-Stokes turbulence models are assessed and compared with the LES results.

  15. A phase II study of neoadjuvant gemcitabine plus doxorubicin in stage IIIB breast cancer: a preliminary report.

    Science.gov (United States)

    Gomez, H; Kahatt, C; Falcon, S; Santillana, S; de Mendoza, F H; Valdivia, S; Vallejos, C; Otero, J; Pen, D L

    2001-06-01

    The purpose of this ongoing study is to determine the response and safety of a combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus doxorubicin as neoadjuvant therapy for stage IIIB breast cancer. Thirty-nine chemotherapy-naive patients were enrolled in the study. The median age was 54 years (range, 32 to 74 years), and the median Karnofsky performance status was 100. Gemcitabine 1,200 mg/m(2) was given on days 1 and 8, and doxorubicin 60 mg/m(2) on day 1, followed by surgery or radiotherapy. Ninety-seven of 117 cycles (83%) were administered at full dose. An overall response rate of 95% was obtained, with a complete response in 18% (seven patients) and a partial response in 77% (30 patients). Twenty-eight patients (72%) underwent breast surgery after a maximum of three cycles of neoadjuvant therapy. World Health Organization grade 3/4 toxicities included leukopenia in nine cycles (8%), neutropenia in 16 cycles (14%), febrile neutropenia in 11 cycles (9%), and anemia in two cycles (2%). The most important nonhematologic toxicity was grade 2/4 mucositis in 16 cycles (14%), and/or grade 2/3 diarrhea in 10 cycles (9%). Neoadjuvant therapy with gemcitabine plus doxorubicin results in a high tumor response rate with moderate oral and hematologic toxicity. Semin Oncol 28 (suppl 10):57-61.

  16. Tadalafil in the treatment of erectile dysfunction

    Directory of Open Access Journals (Sweden)

    Robert M Coward

    2008-12-01

    Full Text Available Robert M Coward, Culley C CarsonDivision of Urologic Surgery, University of North Carolina, Chapel Hill, NC, USAAbstract: The treatment for erectile dysfunction (ED was revolutionized with the development of phosphodiesterase type 5 (PDE5 inhibitors. Tadalafil (Cialis®; Eli Lilly and Company, Indianapolis, IN, USA is the newest and most versatile PDE5 inhibitor in the clinical armamentarium for the treatment of ED. Its most unique characteristic is its long half-life of 17.5 hours, which lends itself to a longer therapeutic window with on-demand dosing and effective steady-state plasma concentrations with once-daily dosing. Clinical trials have proven its safety and efficacy with both dosing strategies for all severities and etiologies of ED, including difficult-to-treat ED. This thorough review will discuss ED, the physiology of penile erection and the role of PDE5, and all aspects of tadalafil, from its development, through its pharmacology, to its latest clinical studies and indications.Keywords: tadalafil, Cialis, PDE5 inhibitors, phosphodiesterase type 5, erectile dysfunction, penile erection

  17. Effects of Low Incoming Turbulence on the Flow around a 5 : 1 Rectangular Cylinder at Non-Null-Attack Angle

    Directory of Open Access Journals (Sweden)

    M. Ricci

    2016-01-01

    Full Text Available The incompressible high Reynolds number flow around the rectangular cylinder with aspect ratio 5 : 1 has been extensively studied in the recent literature and became a standard benchmark in the field of bluff bodies aerodynamics. The majority of the proposed contributions focus on the simulation of the flow when a smooth inlet condition is adopted. Nevertheless, even when nominally smooth conditions are reproduced in wind tunnel tests, a low turbulence intensity is present together with environmental disturbances and model imperfections. Additionally, many turbulence models are known to be excessively dissipative in laminar-to-turbulent transition zones, generally leading to overestimation of the reattachment length. In this paper, Large Eddy Simulations are performed on a 5 : 1 rectangular cylinder at non-null-attack angle aiming at studying the sensitivity of such flow to a low level of incoming disturbances and compare the performance of standard Smagorinsky-Lilly and Kinetic Energy Transport turbulence models.

  18. Proosa 1977. Kirjanduse argipäev / Mall Jõgi

    Index Scriptorium Estoniae

    Jõgi, Mall, 1947-

    2008-01-01

    Sisaldab joonealuseid märkusi ja bibliograafiat. - Varem ilmunud Looming 1978, nr. 2. - Ülevaade 1977. aastal ilmunud eesti proosast. Käsitletakse järgmisi autoreid ja nende teoseid: Ustav Mikelsaar "Ohver", Lembit Kivisaar "Vana diivan", Albert Uustulnd "Avali väraval", Asta Põldmäe "Me", Lilli Promet "Tüdrukud taevast", Nikolai Baturin "Leiud kajast", Aadu Hint "Oma saar", Paul Kuusberg "Linnukesega", Aimée Beekman "Sugupuu", Mari Saat "Mida teha emaga?", Veera Saar "Isa niinepuu", Villem Gross "Vaikimise motiivid", Jüri Tuulik "Meretagune asi", Aira Kaal "Teedla Riia aknas põleb tuli", Tõnis Lehtmets "Tume laas", Väino Ilus "Kinsli peremehed", Einar Maasik "Hispaania tants", Aino Müür "Linnuvere lugu", Jaan Kross "Kolme katku vahel" 3. osa, Endel Nirk "Kaanekukk", Paul Kuusberg "Võõras või õige mees", Toomas Vint "Perekondlikud mängud", Ine Viiding "Kümme käsku kaaskodanikele", Mats Traat "Irdinimene. Türgi oad", Teet Kallas "Õhtuvalgus", Teet Kallas "Insener Paberiti juhtum", Einar Maasik "Üksinda detsembris", Enn Vetemaa "Hõbedaketrajad", Herta Laipaik "Kummitus muusikatoas. Doktor Vallaku mõistatus", Raimond Kaugver "Külalisteraamat"

  19. Flying in Two Dimensions

    CERN Document Server

    Prakash, Manu

    2011-01-01

    Diversity and specialization of behavior in insects is unmatched. Insects hop, walk, run, jump, row, swim, glide and fly to propel themselves in a variety of environments. We have uncovered an unusual mode of propulsion of aerodynamic flight in two dimensions in Waterlilly Beetles \\emph{(Galerucella)}. The adult beetles, often found in water lilly ponds, propel themselves strictly in a two-dimensional plane on the surface of water via flapping wing flight. Here we analyze the aerodynamics of this peculiar flight mode with respect to forces exerted on the organism during flight. The complexity of 2-D flight is captured by accounting for additional forces beyond gravitational, thrust, lift and drag, exerted on the insect body in 3D flight. Understanding this constrained propulsion mode requires accounting for viscous drag, surface tension, buoyancy force, and capillary-wave drag. Moreover, dramatic differences exist in the magnitude of the resultant forces in 2D vs. 3D flight. Here, in this fluid dynamics video...

  20. Common plant toxicology: a comparison of national and southwest Ohio data trends on plant poisonings in the 21st century.

    Science.gov (United States)

    Petersen, Dan D

    2011-07-15

    Data from the American Association of Poison Control Centers (AAPCC) and the Cincinnati-based Drug and Poison Information Center (DPIC) were analyzed to determine the incidence and trends of human plant poisonings since the year 2000. Approximately 3.4% of the approximately 4.3 million annual calls to the AAPCC centers involved plants, with a higher fraction (4.5%) for pediatric exposures. Nearly 70% of plant exposures occurred in children under six. Only 8% of cases required treatment in a health-care facility, and only 0.1% (in 2008) were considered severe outcomes. The most prominent groups of plants involved in exposures are those containing oxalates, and the most common symptom is gastroenteritis. The top 12 identified plants (in descending order) nationally were Spathiphyllum species (peace lilly), Philodendron species (philodendron), Euphorbia pulcherrima (poinssettia), Ilex species (holly), Phytolacca americana (pokeweed), Toxicodendron radicans (poison ivy), Capsicum (pepper), Ficus (rubber tree, weeping fig), Crassula argentea (jade plant), Diffenbachia (dumb cane), Epipremnum areum (pothos) and Schlumbergera bridesii (Christmas cactus). Broad overlaps between the DPIC and the AAPCC incidence data were noted, with essentially the same plant species in each dataset. The nature of the various toxins, the symptomatology and potential treatments are discussed for the highest ranking plant species. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Skoneczna, Iwona; Kerst, J Martijn

    2015-01-01

    BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcin...... patient data meta-analysis and biomarker research are needed to further elucidate the potential for survival benefit in subgroups of patients. FUNDING: Lilly, Canadian Cancer Society Research.......BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial......, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint...

  2. WENDI: A tool for finding non-obvious relationships between compounds and biological properties, genes, diseases and scholarly publications

    Directory of Open Access Journals (Sweden)

    Zhu Qian

    2010-08-01

    Full Text Available Abstract Background In recent years, there has been a huge increase in the amount of publicly-available and proprietary information pertinent to drug discovery. However, there is a distinct lack of data mining tools available to harness this information, and in particular for knowledge discovery across multiple information sources. At Indiana University we have an ongoing project with Eli Lilly to develop web-service based tools for integrative mining of chemical and biological information. In this paper, we report on the first of these tools, called WENDI (Web Engine for Non-obvious Drug Information that attempts to find non-obvious relationships between a query compound and scholarly publications, biological properties, genes and diseases using multiple information sources. Results We have created an aggregate web service that takes a query compound as input, calls multiple web services for computation and database search, and returns an XML file that aggregates this information. We have also developed a client application that provides an easy-to-use interface to this web service. Both the service and client are publicly available. Conclusions Initial testing indicates this tool is useful in identifying potential biological applications of compounds that are not obvious, and in identifying corroborating and conflicting information from multiple sources. We encourage feedback on the tool to help us refine it further. We are now developing further tools based on this model.

  3. Exploring the association between color-blind racial ideology and multicultural counseling competencies.

    Science.gov (United States)

    Neville, Helen; Spanierman, Lisa; Doan, Bao-Tran

    2006-04-01

    The authors examined the association between color-blind racial ideology and self-reported multicultural counseling competencies in 130 applied psychology students and mental health workers. Results from 1 sample (n = 79) indicated that greater levels of color-blind racial ideology as measured by the Color-Blind Racial Attitudes Scale (Neville, Lilly, Duran, Lee, & Browne, 2000) were (1) related to lower self-reported multicultural counseling awareness and knowledge as measured by the Multicultural Counseling Knowledge and Awareness Scale (MCKAS; Ponterotto, Gretchen, Utsey, Rieger, & Austin, 2002) and (2) accounted for a significant amount of variance in MCKAS scores over and above that explained by self-reported multicultural training, social desirability, and participant race. Findings from another sample also provided empirical support for the link between higher color-blind racial ideology and lower multicultural case conceptualization ability (n = 51), after controlling for the influence of the number of multicultural course(s) taken. Implications of the findings and future directions are provided.

  4. Open Innovation Drug Discovery (OIDD): a potential path to novel therapeutic chemical space.

    Science.gov (United States)

    Alvim-Gaston, Maria; Grese, Timothy; Mahoui, Abdelaziz; Palkowitz, Alan D; Pineiro-Nunez, Marta; Watson, Ian

    2014-01-01

    The continued development of computational and synthetic methods has enabled the enumeration or preparation of a nearly endless universe of chemical structures. Nevertheless, the ability of this chemical universe to deliver small molecules that can both modulate biological targets and have drug-like physicochemical properties continues to be a topic of interest to the pharmaceutical industry and academic researchers alike. The chemical space described by public, commercial, in-house and virtual compound collections has been interrogated by multiple approaches including biochemical, cellular and virtual screening, diversity analysis, and in-silico profiling. However, current drugs and known chemical probes derived from these efforts are contained within a remarkably small volume of the predicted chemical space. Access to more diverse classes of chemical scaffolds that maintain the properties relevant for drug discovery is certainly needed to meet the increasing demands for pharmaceutical innovation. The Lilly Open Innovation Drug Discovery platform (OIDD) was designed to tackle barriers to innovation through the identification of novel molecules active in relevant disease biology models. In this article we will discuss several computational approaches towards describing novel, biologically active, drug-like chemical space and illustrate how the OIDD program may facilitate access to previously untapped molecules that may aid in the search for innovative pharmaceuticals.

  5. Development of a statistical tool for the estimation of riverbank erosion probability

    Science.gov (United States)

    Varouchakis, Emmanouil

    2016-04-01

    Riverbank erosion affects river morphology and local habitat, and results in riparian land loss, property and infrastructure damage, and ultimately flood defence weakening. An important issue concerning riverbank erosion is the identification of the vulnerable areas in order to predict river changes and assist stream management/restoration. An approach to predict areas vulnerable to erosion is to quantify the erosion probability by identifying the underlying relations between riverbank erosion and geomorphological or hydrological variables that prevent or stimulate erosion. In the present work, a innovative statistical methodology is proposed to predict the probability of presence or absence of erosion in a river section. A physically based model determines the locations vulnerable to erosion by quantifying the potential eroded area. The derived results are used to determine validation locations for the evaluation of the statistical tool performance. The statistical tool is based on a series of independent local variables and employs the Logistic Regression methodology. It is developed in two forms, Logistic Regression and Locally Weighted Logistic Regression, which both deliver useful and accurate results. The second form though, provides the most accurate results as it validates the presence or absence of erosion at all validation locations. The proposed tool is easy to use, accurate and can be applied to any region and river. Varouchakis, E. A., Giannakis, G. V., Lilli, M. A., Ioannidou, E., Nikolaidis, N. P., and Karatzas, G. P.: Development of a statistical tool for the estimation of riverbank erosion probability, SOIL (EGU), in print, 2016.

  6. MAL/VIP17, a new player in the regulation of NKCC2 in the kidney.

    Science.gov (United States)

    Carmosino, Monica; Rizzo, Federica; Procino, Giuseppe; Basco, Davide; Valenti, Giovanna; Forbush, Biff; Schaeren-Wiemers, Nicole; Caplan, Michael J; Svelto, Maria

    2010-11-15

    The renal-specific Na+-K+-2Cl- cotransporter (NKCC2) is the major salt transport pathway of the apical membrane of the mammalian thick ascending limb of Henle's loop. Here, we analyze the role of the tetraspan protein myelin and lymphocytes-associated protein (MAL)/VIP17 in the regulation of NKCC2. We demonstrated that 1) NKCC2 and MAL/VIP17 colocalize and coimmunoprecipitate in Lilly Laboratories cell porcine kidney cells (LLC-PK1) as well as in rat kidney medullae, 2) a 150-amino acid stretch of NKCC2 C-terminal tail is involved in the interaction with MAL/VIP17, 3) MAL/VIP17 increases the cell surface retention of NKCC2 by attenuating its internalization, and 4) this coincides with an increase in cotransporter phosphorylation. Interestingly, overexpression of MAL/VIP17 in the kidney of transgenic mice results in cysts formation in distal nephron structures consistent with the hypothesis that MAL/VIP17 plays an important role in apical sorting or in maintaining the stability of the apical membrane. The NKCC2 expressed in these mice was highly glycosylated and phosphorylated, suggesting that MAL/VIP17 also is involved in the stabilization of NKCC2 at the apical membrane in vivo. Thus, the involvement of MAL/VIP17 in the activation and surface expression of NKCC2 could play an important role in the regulated absorption of Na+ and Cl- in the kidney.

  7. Vitamin levels in adults with ADHD

    Science.gov (United States)

    Landaas, Elisabeth Toverud; Aarsland, Tore Ivar Malmei; Ulvik, Arve; Halmøy, Anne; Ueland, Per Magne; Haavik, Jan

    2016-01-01

    Background Micronutrients containing vitamins are reported to reduce symptom levels in persons with attention-deficit hyperactivity disorder (ADHD), but data on vitamin levels in ADHD are sparse. Aims To examine the relationship between vitamin concentrations, ADHD diagnosis and psychiatric symptoms in young adult ADHD patients and controls. Method Eight vitamins and the nicotine metabolite cotinine were analysed in serum samples from 133 ADHD patients and 131 controls aged between 18 and 40, who also reported ADHD symptoms and comorbid conditions. Results Lower concentrations of vitamins B2, B6 and B9 were associated with the ADHD diagnosis, and B2 and B6 also with symptom severity. Smokers had lower levels of vitamins B2 and B9. Conclusions ADHD patients were overrepresented in the group with low levels of some vitamins, possibly indicative of inadequate dietary intake of these micronutrients in a subgroup of patients. It is important to identify these patients in dietary intervention trials of ADHD. Declaration of interest J.H. has received lecture honoraria as part of continuing medical education programmes sponsored by Novartis, Eli Lilly and Company, and Janssen-Cilag. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:27990293

  8. Baricitinib: First Global Approval.

    Science.gov (United States)

    Markham, Anthony

    2017-03-13

    Baricitinib (Olumiant™) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus. JAKs transduce intracellular signals from cell surface receptors for various cytokines and growth factors involved in inflammation and immune function, suggesting JAK inhibitors may be of therapeutic benefit in inflammatory conditions. In February 2017, baricitinib was approved in the EU, as monotherapy or in combination with methotrexate, for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Regulatory approval to market baricitinib as a treatment for RA has also been sought in the USA and Japan. This article summarizes the milestones in the development of baricitinib leading to this first global approval for the treatment for moderate to severe active RA in adult patients who have responded inadequately to, or are intolerant to one or more DMARDs.

  9. The story of insulin discovery.

    Science.gov (United States)

    Karamitsos, Dimitrios T

    2011-08-01

    Many researchers had tried to isolate insulin from animal pancreas, but Frederick Banting, a young surgeon, and Charles Best, a medical student, were the ones that succeeded. They both worked hard in very difficult conditions in the late 1921 and early 1922 until final success. They encountered problems with the impurities of their extract that was causing inflammations, but J. Collip, their late biochemist collaborator, worked many hours and was soon able to prepare cleaner insulin, free from impurities. This extract was administered successfully to L. Thomson, a ketotic young diabetic patient, on 23 January 1922. Following this, Eli Lilly & Co of USA started the commercial production of insulin, soon followed by the Danish factories Nordisc and NOVO as well as the British Wellcome. Nicolae Paulescu who was professor of Physiology in Bucharest, was also quite close to the discovery of insulin but the researchers in Toronto were faster and more efficient. Banting and Macleod won the Nobel price, which Banting shared with Best and Macleod with J. Collip. The contribution of Paulescu in insulin discovery was recognized after his death. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Insulin: Almost a Century of Lifesaving.

    Science.gov (United States)

    2017-04-01

    The identification and purification of insulin in 1922 changed life for individuals with type 1 diabetes mellitus (T1DM). Its discovery was, to a certain extent, serendipitous. Although medical researchers suspected that some type of hormone was responsible for carbohydrate metabolism, by the end of the 19th century they had made little progress. When World War I broke out, efforts stalled. A somewhat cantankerous group of Canadian researchers led by Frederick Grant Banting, a surgeon, are credited with insulin's discovery. Their initial research was discredited and criticized for poor technique. Regardless, they persevered, and in January 1922 they successfully treated their first patient. A mere nine months later, collaboration between the University of Toronto and Eli Lilly Company made insulin available in North America. Derived from beef and pork pancreases, the 40 unit/mL product little resembled today's more refined human insulin. While insulin is indispensable to individuals with T1DM, it is also used or being studied for several different conditions. Some researchers have dubbed Alzheimer's disease "type 3 diabetes" because of similar aberrations in the blood-brain barrier and protein deposits.

  11. Industrial demand side management status report - synopsis

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.E.F.; Conger, R.L.; Foley, T.J. [and others

    1996-05-01

    Industrial demand side management (DSM) programs, though not as developed or widely implemented as residential and commercial programs, hold the promise of significant energy savings-savings that will benefit industrial firms, utilities and the environment. This paper is a synopsis of a larger research report, Industrial Demand Side Management: A Status Report, prepared for the U.S. Department of Energy. The report provides an overview of and rationale for DSM programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential electricity savings from industrial energy efficiency measures. Overcoming difficulties to effective program implementation is worthwhile, since rough estimates indicate a substantial potential for electricity savings. The report categorizes types of DSM programs, presents several examples of each type, and explores elements of successful programs. Two in-depth case studies (of Boise Cascade and of Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. Finally, the research report also includes a comprehensive bibliography, a description of technical assistance programs, and an example of a methodology for evaluating potential or actual savings from projects.

  12. Industrial demand side management status report: Synopsis

    Energy Technology Data Exchange (ETDEWEB)

    Hopkins, M.E.F.; Conger, R.L.; Foley, T.J.; Parker, J.W.; Placet, M.; Sandahl, L.J.; Spanner, G.E.; Woodruff, M.G.; Norland, D.

    1995-08-01

    Industrial demand side management (DSM) programs, though not as developed or widely implemented as residential and commercial programs, hold the promise of significant energy savings-savings that will benefit industrial firms, utilities and the environment. This paper is a synopsis of a larger research report, Industrial Demand Side Management. A Status Report, prepared for the US Department of Energy. The report provides an overview of and rationale for DSM programs. Benefits and barriers are described, and data from the Manufacturing Energy Consumption Survey are used to estimate potential electricity savings from industrial energy efficiency measures. Overcoming difficulties to effective program implementation is worthwhile, since rough estimates indicate a substantial potential for electricity savings. The report categorizes types of DSM programs, presents several examples of each type, and explores elements of successful programs. Two in-depth case studies (of Boise Cascade and of Eli Lilly and Company) illustrate two types of effective DSM programs. Interviews with staff from state public utility commissions indicate the current thinking about the status and future of industrial DSM programs. Finally, the research report also includes a comprehensive bibliography, a description of technical assistance programs, and an example of a methodology for evaluating potential or actual savings from projects.

  13. Estudo histológico e histoquímico da glândula de Duvernoy de Clelia plumbea (Wied (Serpentes, Colubridae, Xenodontinae Histological and histochemical study of Duvernoy's gland from Clelia plumbea (Wied (Serpentes, Colubridae, Xenodontinae

    Directory of Open Access Journals (Sweden)

    Márcia Ferret Renner

    2000-09-01

    Full Text Available There are report two human envenenomations for species from Clelia Fitzinger, 1826 (opisthoglyph snake. The patients exhibited symptoms similar from bothropic accident. Then this work have with objective, the hystological and histochemical study of Duvernoy's gland from Clelia plumbea. For the hystological observation of the Duvernoy's gland were using, with paraffin's cutting edge, two methods: Hematoxylin + Eosin and Toluidine's Blue. With historesine's cutting edge were using three methods: Metilen's Blue, Toluidine's Blue + Floxine and Toluidine's Blue. For the histochemical detection were using six techniques, with paraffin's cutting edge: PAS, PAS + Alcian Blue pH 2,5, Alcian Blue pH 2,5, PAS + Salivar Amilase, Method of Lars Grimelius and Method of Lillie. It was evidenced the predominance of serous cells on Duvernoy's gland. In relation to the histochemical constituion of the duvernoy's gland, was verified the presence of glucoconjugates neuters, enzymes and cells with reduetive activity. By fact from this species to kill his preys by constriction, the predominance of serous cells in the duvernoy's gland, don' t must be direct related with the subjugation of his preys, but with the digestive processes. Histological and histochemical analysis showed cells of Duvernoy's gland are constituted for two populations: serous cells (prodution of enzymes and mucous cells (prodution of glucoconjugates.

  14. Production of β-1,3-glucanase and chitinase of two biocon trol agents and their possible modes of action

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Pichia membranefaciens Hansen and Candida guilliermondii(Cast) Langeronet Guerra are two antagonists of R. stolonifer on harvested nectarine and peach fruits. In this study, β-1,3-glucanase and chitinase activities of the antagonists were induced in vitro and in vivo. The highest β-1,3-glucanase activity was detected in Lilly-Barnett minimal salt medium supplemented with glucose in combination with CWP of R. stolonifer as a carbon source. The β-1,3-glucanase activity of P. membranefaciens reached the maximum level,being 114.0 SU (specific activity unit), and that of C. guilliermondii reached 103.2 SU. The lowest β-1,3-glucanase activity was observed in the medium containing glucose as sole carbon source. P. membranefaciens was able to produce significantly higher levels of chitinase (exochitinase and endochitinase) in vitro than C. guilliermondii grown in Czapeck minimal medium. An increase in β-1,3-glucanase and chitinase activity was also triggered by wounding, adding of carbon sources and yeast cells. The results showed that both β-1,3-glucanase and chitinase from P. membranefaciens and C. guilliermondii exhibited some effects on controlling R.stolonifer, and might have a synergistic activity against R.stolonifer.

  15. Evaluation of microfluidics reactor technology on the kinetics of virus inactivation.

    Science.gov (United States)

    Bailey, Mark R; Chen, Dayue; Emery, Warren R; Lambooy, Peter K; Nolting, Juliana; Quertinmont, Michelle T; Shamlou, Parviz A

    2008-04-15

    Mammalian cell lines constitute an important part in the manufacture of therapeutic proteins. However, their susceptibility to virus contamination is a potential risk to patient safety and productivity, and has led to the development of a repertoire of virus inactivation techniques. From a process development viewpoint, the challenge is to demonstrate the required log reduction in virus content without a significant loss in product titer or quality. The balance between the two is dictated by the kinetics of virus inactivation and protein degradation, both of which are critically affected by process parameters. In this study we describe a commercially available microchannel reactor (MCR) and demonstrate how it can be used to evaluate the impact of temperature on the kinetics of virus inactivation and protein product degradation. Virus spiking experiments are reported using Xenotropic Murine Leukemia Virus and REOvirus, into buffers in the absence and presence of a therapeutic protein currently under development at Lilly. The results demonstrate that the MCR is an ideal platform for evaluation of fast reactive systems and reactions that are particularly sensitive to small changes to process conditions. These conditions include heat inactivation of a virus in a mammalian cell culture process stream used in the manufacture of therapeutic proteins and antibodies.

  16. Progress in the prediction of non-unity Prandtl-number turbulent flows using TransAT

    Energy Technology Data Exchange (ETDEWEB)

    Lakehal, D.; Panyasantisuk, J.; Caviezel, D.; Labois, M.; Narayanan, C., E-mail: lakehal@ascomp.ch [ASCOMP GmbH Zurich (Switzerland)

    2011-07-01

    We report LES results of the flow and convective heat transfer in a heated channel at a wall shear Reynolds number of Reτ = 150 and 171. The results are compared with available DNS data for various Prandtl number fluids (Pr = 0.1-10). In order to deal with non-unity Pr fluid flows, we have extended the variant of the Dynamic sub-grid scale (SGS) model of Germano proposed by Lilly to the thermal field, whereby the motion of the unresolved fluid flow and thermal structures is dictated by the resolved thermal-flow field. The base LES strategy as built in the code TransAT has been first validated for a practical case: the thermal-flow in a T junction, showing time-averaged results with excellent agreement with the experiment. The extended SGS model to the thermal field delivers results in line with the DNS data of a heated channel flow, and reveals that the turbulent Prandtl number cannot be fixed in an ad-hoc manner, and is clearly dependent on both the fluid and flow properties. (author)

  17. International investment agreements and public health: neutralizing a threat through treaty drafting.

    Science.gov (United States)

    Mercurio, Bryan

    2014-07-01

    The high profile investment claims filed by Philip Morris challenging Uruguayan and Australian measures that restrict advertising and logos on tobacco packaging awakened the public health community to the existence and potential detrimental impact of international investment agreements (IIAs). More recently, Eli Lilly challenged Canada's invalidation of a pharmaceutical patent under an IIA. All of the cases claim that the intellectual property rights of the investor were infringed. As a result of these cases, many commentators and activists view IIAs as a threat to public health and have lobbied against their inclusion in ongoing trade negotiations. This article does not argue against IIAs. Instead, it seeks to demonstrate how more sophisticated treaty drafting can neutralize the threat to public health. In this regard, the article seeks to engage members of the public health community as campaigners not against IIAs but as advocates of better treaty drafting to ensure that IIAs do not infringe upon the right of a nation to take non-discriminatory measures for the promotion and protection of the health of their populations.

  18. Pharma Success in Product Development—Does Biotechnology Change the Paradigm in Product Development and Attrition.

    Science.gov (United States)

    Evens, Ronald P

    2016-01-01

    The biotechnology segment of the overall biopharma industry has existed for only about 40–45 years, as a driver of new product development. This driving force was initiated with the FDA approval of recombinant human insulin in 1982, originating from the Genentech company. The pharma industry in the early years of 1970s and 1980s engaged with biotechnology companies only to a small extent with their in-licensing of a few recombinant molecules, led by Roche, Eli Lilly, and Johnson and Johnson. However, subsequently and dramatically over the last 25 years, biotechnology has become a primary driver of product and technology innovation and has become a cornerstone in new product development by all biopharma companies. This review demonstrates these evolutionary changes regarding approved products, product pipelines, novelty of the products, FDA approval rates, product sales, financial R&D investments in biotechnology, partnerships, mergers and acquisitions, and patent issues. We now have about 300 biotechnology products approved in USA covering 16 medical disciplines and about 250 indications, with the engagement of 25 pharma companies, along with their biotechnology company innovators and partners. The biotechnology pipeline involves over 1000 molecules in clinical trials, including over 300 molecules associated with the top 10 pharma companies. Product approval rates by the FDA for biotechnology products are over double the rate for drugs. Yes, the R&D paradigm has changed with biotechnology now as one of the major focuses for new product development with novel molecules by the whole biopharma industry.

  19. Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: a dermatology-oncology perspective.

    Science.gov (United States)

    Lacouture, M E; Melosky, B L

    2007-01-01

    The epidermal growth factor receptor (EGFR) is often overexpressed or dysregulated in solid tumors. Targeting the EGFR-mediated signaling pathway has become routine practice in the treatment of lung, pancreatic, head and neck, and colon carcinomas. Available agents with selected activity towards the EGFR include low molecular weight tyrosine kinase inhibitors, e.g., erlotinib (Tarceva, Genentech BioOncology/ OSI Pharmaceuticals/ F. Hoffmann-La Roche) and monoclonal antibodies, such as cetuximab (Erbitux, Bristol-Myers Squibb/ ImClone Systems/ Merck) and panitumumab (Vectibix, Amgen). Their use is anticipated to increase for treating other solid tumors that are dependent on this pathway for growth and proliferation. Health Canada and the US FDA have approved erlotinib for the treatment of advanced non-small cell lung carcinoma (NSCLC). It has also been approved in the US for use against pancreatic cancer in combination with gemcitabine (Gemzar, Eli Lilly). Cetuximab and most recently panitumumab (Vectibix, Amgen/ Abgenix) were approved by the US FDA for metastatic colorectal carcinoma. Cetuximab is also approved in the US for head and neck squamous cell carcinoma. The safety profile for this class of drugs is unique, with virtually no hematological toxicity, but frequent cutaneous and gastrointestinal side-effects. Although there is a dearth of randomized trials addressing treatment of the dermatological side-effects, some basic principles of management have been agreed upon and can likely improve patient compliance and decrease inappropriate dose reduction, which may negatively influence the antitumor effect.

  20. Computer-aided process analysis and economic evaluation for biosynthetic human insulin production-A case study.

    Science.gov (United States)

    Petrides, D; Sapidou, E; Calandranis, J

    1995-12-05

    Human insulin was the first mammalian protein produced in bacteria using recombinant DNA technology. Two technologies were developed; the first based on the separate expression of precursors of chains A and B of insulin, and the second based on the expression of a precursor of proinsulin as a Trp-E fusion protein. Both technologies utilized Escherichia coli as an expression system. Later, a third technology was developed based on a strain of yeast that can secrete a precursor of insulin. The second E. coli process, a variation of which has been commercialized by Eli Lilly and Co., is analyzed in this article from a process design and economic evaluation viewpoint. The objective of this work is to elucidate the technical complexity and high cost associated with the manufacturing of biopharmaceuticals. Human insulin is a good example of a protein-based biopharmaceutical produced in large quantities (a fex tons per year) that requires large scale equipment and presents a multitude of scale-up challenges. Based onthe analysis, a number of conclusions are drawn regarding the cost breakdown and cost dependency on process parameters. Recommendations are made for cost reduction and environmental impact minimization. This analysis was performed using a software tool for computer-aided bioprocess design. (c) 1995 John Wiley & Sons, Inc.

  1. [Effect of vincristine on molar development and jaw growth in rats].

    Science.gov (United States)

    Sedlecki, S; Jakovljević, A; Pap, K

    1989-01-01

    A cystostatic of group Vinca-alcaloides, Vincristine, is often used in chemotherapy. As a microtubular poison it reacts with microtubular molecules of cell cytoplasma and in response to dose administrated decelerates or stops cell division. Since the information about the effect of this drug on molar teeth has not been found in available literature the aim of this study was to investigate the effect of vincristine on tooth development and jaw growth in rats. The experiment was carried out on Wistar rats of both sexes. Vincristine (Oncovin, "Lilly") was injected to animals in the dose of 0.1 mg/kg b.w. seven or eight days following birth. Treated and control animals were sacrificed on the 24th postnatal day. Radiographs of the mandibule were used to study tooth development. The morphometric examination concerned the following parameters: in maxillar frontal and posterior arc width and height; vertical and sagital dimension as well as length of incisive crown in the mandibule. The results of the analysis suggested that the teeth of treated rats were retarded in development compared to the control animals. Morphometric investigations showed that in treated rats both jaws were decelerated in growth in comparison to the control group but with no statistical significance. It should be emphasized that a 16-day-period was too short that full efficet of Vincristine should be established in rats and lead to a result which could suggest a certain molar development and jaw growth.

  2. Proton milliprobe analyses of the Gutenberg Bible

    Science.gov (United States)

    Kusko, Bruce H.; Cahill, Thomas A.; Eldred, Robert A.; Schwab, Richard N.

    1984-04-01

    The advent of printing with movable type is properly regarded as the most important technological event in modern cultural history, yet its earliest history is shrouded in mystery. The Davis proton milliprobe has enabled scientists and humanist scholars to collaborate in unlocking the secrets of earliest print, focusing on the contribution of Johannes Gutenberg. The 42-line Gutenberg Bible is not only the first book printed by movable type, it is considered by many to be the finest book every printed. Unfortunately very little is known about the materials and techniques used in this first large scale printing operation. In October 1982 we had the unprecedented opportunity to examine page-by-page the inks, papers, illuminations and binding of volume I of the Doheny Gutenberg Bible. A similar study of the Lilly New Testament (most of volume II) was undertaken in March 1983. The results, some wholly unexpected and very exciting, add a large new body of information about this great work, and give us new enlightenment on the day-to-day production of this first and most important printed book. Moreover, the discovery of the uniqueness of the ink in Gutenberg's Bible, combined with our ability to taken minutely detailed and non-destructive elemental "fingerprints" with the milliprobe beam of all man-made papers and inks, gives us a weapon that has never been available before to investigate some of the controversial basic questions in the history of the origins of printing technology.

  3. The mass-metallicity and fundamental metallicity relations at z>2 using VLT and Subaru near-infrared spectroscopy of zCOSMOS galaxies

    CERN Document Server

    Maier, C; Ziegler, B; Contini, T; Montero, E Perez; Peng, Y; Balestra, I

    2014-01-01

    In the local universe, there is good evidence that, at a given stellar mass M, the gas-phase metallicity Z is anti-correlated with the star formation rate (SFR) of the galaxies. It has also been claimed that the resulting Z(M,SFR) relation is invariant with redshift - the so-called Fundamental Metallicity Relation (FMR). Given a number of difficulties in determining metallicities, especially at higher redshifts, the form of the Z(M,SFR) relation and whether it is really independent of redshift is still very controversial. To explore this issue at z>2, we used VLT-SINFONI and Subaru-MOIRCS near-infrared spectroscopy of 20 zCOSMOS-deep galaxies at 2.12 galaxies of a given mass have much higher SFRs than the local SDSS galaxies. We find that the zCOSMOS galaxies are consistent with a non-evolving FMR if we use the physically-motivated formulation of the Z(M,SFR) relation from Lilly et al. (2003), but not if we use the empirical formulation of Mannucci et al. (2010).

  4. Oxygen abundances of zCOSMOS galaxies at z ~ 1.4 based on five lines and implications for the fundamental metallicity relation

    Science.gov (United States)

    Maier, Christian; Lilly, Simon J.; Ziegler, Bodo L.

    2015-02-01

    A relation between the stellar mass M and the gas-phase metallicity Z of galaxies, the MZR, is observed up to higher redshifts. It is a matter of debate, however, if the SFR is a second parameter in the MZR. To explore this issue at z > 1, we used VLT-SINFONI near-infrared (NIR) spectroscopy of eight zCOSMOS galaxies at 1.3 extinction corrected Hα measurements. We find that the MZR of these star-forming galaxies at z ~ 1.4 is lower than the local SDSS MZR by a factor of three to five, a larger change than reported in the literature using [NII]/Hα-based metallicities from individual and stacked spectra. Correcting N2-based O/Hs using recent results by Newman et al. (2014), also the larger FMOS sample at z ~ 1.4 of Zahid et al. (2014) shows a similar evolution of the MZR like the zCOSMOS objects. These observations seem also in agreement with a non-evolving FMR using the physically motivated formulation of the FMR from Lilly et al. (2013).

  5. Physicochemical Requirement for the Vegetative Growth of Schizophyllum commune Collected from Different Ecological Origins

    Science.gov (United States)

    Imtiaj, Ahmed; Jayasinghe, Chandana; Lee, Geon Woo; Kim, Hye Young; Shim, Mi Ja; Rho, Hyun-Su; Lee, Hyun Sook; Hur, Hyun; Lee, Min Woong; Lee, U-Youn

    2008-01-01

    Schizophyllum commune is an edible and medicinal mushroom widely distributed in the world. The optimal growth conditions for the mycelia of 10 strains of the fungus were investigated. The temperature suitable for the mycelial growth and density was obtained at 30~35℃. Among the tested conditions, the minimum mycelial growth was found at 15℃. In case of pH, the most favorable growth was found at pH 5. The results indicated that this mushroom well adapted to high temperature and low pH for its mycelial growth. Considering growth phenotype of mycelia, Hamada, Hennerberg, PDA and YM were the most suitable and Lilly, Glucose triptone, Glucose peptone and Hoppkins were the most unfavorable among tested media for the mycelial growth of S. commune. Out of tested carbon sources, dextrin and fructose were the most suitable and lactose, mannose and sorbitol were the unsuitable for the fungus. Compact mycelial density was obtained from most of the carbon sources. Among used nitrogen sources, calcium nitrate, potassium nitrate and alanine were the most appropriate and the most incompatible were ammonium phosphate, histidine, urea and arginine for mycelial growth of S. commune on the culture media. Calcium nitrate, histidine and potassium nitrate showed moderately thin or thin, and rest of nitrogen sources showed compact or moderately compact mycelial density. PMID:23997605

  6. Short outlines of books by Estonian authors / Janika Kronberg, Rutt Hinrikus

    Index Scriptorium Estoniae

    Kronberg, Janika, 1963-

    2003-01-01

    Sinijärv, Karl- Martin. Artutart & 39. Tallinn : Tuum, 2002 ; Beier, Priidu. Monaco. Tartu : P. Beier, 2002 ; Malin, Jaan. Sulle. Tartu : J. Malin, 2003 ; Liiv, Toomas. Luuletused 1968-2002. Tallinn : Tuum, 2003 ; Mägi, Arvo. Katk ja koolera. Tartu : Ilmamaa ; Kross, Jaan. Omaeluloolisus ja alltekst. Tallinn : Eesti Keele Sihtasutus, 2003 ; Kaplinski, Jaan ; Salminen, Johannes. Ööd valged ja mustad. Tallinn : Loomingu Raamatukogu, 2003 ; Kauksi Ülle. Käänüpäiv. Tartu : Kauksi Ülle Mänedsment', 2003 ; Luik, Tõnu. Filosoofiast kõnelda. Tartu : Ilmamaa, 2002 ; Teder, Tarmo. Pööningujutud. Tallinn : Eesti Keele Sihtasutus, 2002 ; Vetemaa, Enn. Minu väga magus elu ehk martsipanimeister. Tallinn : Tänapäev, 2002 ; Põldroos, Enn. Joonik kivi. Tallinn : Eesti Keele Sihtasutus, 2003 ; Suburg, Lilli. Kogutud kirjatööd. Tallinn : Eesti Raamat, 2002 ; Mikelsaar, Henn. Müüritud. Tartu : Ilmamaa, 2003 ; Kaus, Jan. Õndsate tund. Tallinn : Tuum, c2003

  7. Pioglitazone has a dubious bladder cancer risk but an undoubted cardiovascular benefit.

    Science.gov (United States)

    Ryder, R E J

    2015-03-01

    On 8 April 2014, a US jury ordered Takeda and Eli Lilly to pay $9 bn in punitive damages after finding that they had concealed the cancer risks associated with pioglitazone. By contrast, on 28 August 2014, the long-awaited outcome of the 10-year Kaiser Permanente Northern California study was announced. That study was specifically designed to investigate whether patients exposed to pioglitazone were at an increased risk of bladder cancer and found no association; thus, at last, the controversial issue has been resolved. A review, in retrospect, of the story of the proposed link between pioglitazone and bladder cancer reveals flaws at every stage. In 2012, a BMJ editorial, in keeping with some other contemporary reports, stated 'it can confidently be assumed that pioglitazone increases the risk of bladder cancer'. Examination of the information which led to such a statement shows that: 1) the pre-clinical findings of bladder cancer in male rats is not indicative of human risk; 2) there is no association between bladder cancer and pioglitazone in randomized controlled trials, once cases that could not plausibly be related to treatment are removed; and 3) the observational studies that have suggested a link have over-extrapolated from the data: pioglitazone-treated patients had more risk factors for bladder cancer than those not treated with pioglitazone. Meanwhile careful study of randomized controlled trials shows evidence of cardiovascular benefit from pioglitazone in Type 2 diabetes, a condition which results, more than anything, in premature cardiovascular death and morbidity.

  8. Ampullary organ morphology of freshwater salmontail catfish, Arius graeffei.

    Science.gov (United States)

    Whitehead, D L; Tibbetts, I R; Daddow, L Y

    2000-11-01

    Two types of ampullary organs are present in the skin of the freshwater salmontail catfish, Arius graeffei, each consisting of a short canal (0.2-0.5 mm) oriented perpendicular to the basement membrane and ending in an ampulla. Histochemical staining techniques (Alcian blue and Lillie's allochrome) indicate that the ampullary canals contain an acidic mucopolysaccharide gel, which is uniform in its staining properties along the canals. Type II ampullary organs consist of a canal, the wall of which is lined with cuboidal epithelial cells. The canal opens into an ampulla with 50-60 receptor cells. Electron microscopy reveals that the pear-shaped receptor cells bear microvilli on their luminal surface and lie adjacent to an unmyelinated neuron. Type III ampullary organs differ from Type II in that the canal wall consists of cells that possess a protein-rich sac at the luminal apex and have a polymorphic nucleus. The canals of Type III ampullary organs open to an ampulla with 8-30 receptor cells similar in both staining properties and structure to those of the Type II organ. In both types of ampullary organs, supportive cells surround each receptor cell except at the apex of the receptor cell.

  9. Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial.

    Science.gov (United States)

    Mayfield, Karla; Siskind, Dan; Winckel, Karl; Hollingworth, Samantha; Kisely, Steve; Russell, Anthony W

    2015-06-01

    Clozapine causes significant metabolic disturbances including obesity and type 2 diabetes. Recent evidence that reduced glucagon-like-peptide-1 (GLP-1) may contribute to aetiology of clozapine-associated metabolic dysregulation suggests a potential therapeutic role for GLP-1 agonists. This open-label, pilot randomised controlled trial evaluates the effect of exenatide in clozapine-treated obese adults who have schizophrenia, with or without poorly controlled diabetes. Sixty out-patients will be randomised to once weekly extended release exenatide or treatment as usual for 24 weeks. To evaluate the feasibility of larger studies regarding methodology, acceptability, tolerability and estimate efficacy for glycaemic control or weight loss. Secondary outcomes are psychosis severity and metabolic parameters. This is the first trial investigating GLP-1 agonists for glycaemic control and weight loss in clozapine-treated patients with either diabetes or obesity. Clozapine-associated obesity and diabetes with exenatide (CODEX) will provide proof-of-concept empirical evidence addressing whether this novel treatment is practical and worthy of further investigation. A.W.R. has received speaker honoraria and travel grants from AstraZeneca, BoehringerIngelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and has participated on advisory panels for MSD and Novo Nordisk. © The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

  10. Evaluation of teriparatide treatment in adults with osteogenesis imperfecta

    Science.gov (United States)

    Orwoll, Eric S.; Shapiro, Jay; Veith, Sandra; Wang, Ying; Lapidus, Jodi; Vanek, Chaim; Reeder, Jan L.; Keaveny, Tony M.; Lee, David C.; Mullins, Mary A.; Nagamani, Sandesh C.S.; Lee, Brendan

    2014-01-01

    Background. Adults with osteogenesis imperfecta (OI) have a high risk of fracture. Currently, few treatment options are available, and bone anabolic therapies have not been tested in clinical trials for OI treatment. Methods. 79 adults with OI were randomized to receive 20 μg recombinant human parathyroid hormone (teriparatide) or placebo for 18 months in a double-blind, placebo-controlled trial. The primary endpoint was the percent change in areal bone mineral density (aBMD) of the lumbar spine (LS), as determined by dual-energy X-ray absorptiometry. Secondary endpoints included percent change in bone remodeling markers and vertebral volumetric BMD (vBMD) by quantitative computed tomography, estimated vertebral strength by finite element analysis, and self-reported fractures. Results. Compared with the placebo group, the teriparatide group showed increased LS aBMD (6.1% ± 1.0% vs. 2.8% ± 1.0% change from baseline; P Imperfecta Foundation, Eli Lilly and Co., the National Center for Advancing Translational Science (NCATS) at the NIH (grant no. UL1RR024140), and the Baylor College of Medicine General Clinical Research Center (grant no. RR00188). PMID:24463451

  11. Proosa 1977. Kirjanduse argipäev / Mall Jõgi

    Index Scriptorium Estoniae

    Jõgi, Mall, 1947-

    2008-01-01

    Sisaldab joonealuseid märkusi ja bibliograafiat. - Varem ilmunud Looming 1978, nr. 2. - Ülevaade 1977. aastal ilmunud eesti proosast. Käsitletakse järgmisi autoreid ja nende teoseid: Ustav Mikelsaar "Ohver", Lembit Kivisaar "Vana diivan", Albert Uustulnd "Avali väraval", Asta Põldmäe "Me", Lilli Promet "Tüdrukud taevast", Nikolai Baturin "Leiud kajast", Aadu Hint "Oma saar", Paul Kuusberg "Linnukesega", Aimée Beekman "Sugupuu", Mari Saat "Mida teha emaga?", Veera Saar "Isa niinepuu", Villem Gross "Vaikimise motiivid", Jüri Tuulik "Meretagune asi", Aira Kaal "Teedla Riia aknas põleb tuli", Tõnis Lehtmets "Tume laas", Väino Ilus "Kinsli peremehed", Einar Maasik "Hispaania tants", Aino Müür "Linnuvere lugu", Jaan Kross "Kolme katku vahel" 3. osa, Endel Nirk "Kaanekukk", Paul Kuusberg "Võõras või õige mees", Toomas Vint "Perekondlikud mängud", Ine Viiding "Kümme käsku kaaskodanikele", Mats Traat "Irdinimene. Türgi oad", Teet Kallas "Õhtuvalgus", Teet Kallas "Insener Paberiti juhtum", Einar Maasik "Üksinda detsembris", Enn Vetemaa "Hõbedaketrajad", Herta Laipaik "Kummitus muusikatoas. Doktor Vallaku mõistatus", Raimond Kaugver "Külalisteraamat"

  12. Large-eddy structures of turbulent swirling flows and methane-air swirling diffusion combustion

    Institute of Scientific and Technical Information of China (English)

    Liyuan Hu; Lixing Zhou; Jian Zhang; Keren Wang

    2005-01-01

    Turbulent swirling flows and methane-air swirling diffusion combustion are studied by large-eddy simulation (LES) using a Smagorinsky-Lilly subgrid scale turbulence model and a second-order moment (SOM) SGS combustion model, and also by RANS modeling using the Reynolds Stress equation model with the IPCM+wall and IPCM pressure-strain models and SOM combustion model. The LES statistical results for swirling flows give good agreement with the experimental results, indicating that the adopted subgrid-scale turbulence model is suitable for swirling flows.The LES instantaneous results show the complex vortex shedding pattern in swirling flows. The initially formed large vortex structures soon break up in swirling flows. The LES statistical results of combustion modeling are near the experimental results and are as good as the RANS-SOM modeling results. The LES results show that the size and range of large vortex structures in swirling combustion are different from those of isothermal swirling flows, and the chemical reaction is intensified by the large-eddy vortex structures.

  13. Systematic review of the economic aspects of nonadherence to antipsychotic medication in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Dilla T

    2013-04-01

    Full Text Available Tatiana Dilla, Antonio Ciudad, María ÁlvarezDepartment of Clinical Research and Development, Lilly, S.A. Alcobendas, SpainPurpose: There is strong evidence supporting the link between nonadherence to antipsychotic medication and relapse of schizophrenia. However, less obvious are the economic consequences of nonadherence. The systematic review reported here evaluated the economic aspects of nonadherence to antipsychotic medication.Methods: A systematic review of scientific papers in the PubMed MEDLINE, Embase, PsychINFO, BIOSIS, and Evidence-Based Medicine Reviews databases was undertaken. Studies that measured adherence to antipsychotic medication and that provided comparative information on health care costs were included.Results: Eight studies met the inclusion criteria. All were observational. Despite the differences between the studies in terms of design, adherence measures, and cost components analyzed, the results of this systematic review indicate that nonadherence to antipsychotic medication is associated with increased hospitalization rates and resource utilization, resulting in increased direct health care costs.Conclusion: Nonadherence to antipsychotic medication results in poor health and economic outcomes; therefore, the authors suggest endorsing interventions aimed at improving adherence because they can improve patient health without substantially increasing costs.Keywords: adherence, costs, observational study, hospitalization rates, resource utilization

  14. Bauhäusler on the Franco-Spanish Border

    Directory of Open Access Journals (Sweden)

    Laura Martínez de Guereñu

    2016-10-01

    Full Text Available This article focuses on the travels of Bauhaus masters and instructors and on the transport of Bauhaus products to Spain in 1929, when the Franco-Spanish border was still culturally permeable. Ludwig Mies van der Rohe and Marcel Breuer introduced their tubular-steel furniture in the Spanish market. Mies and Lilly Reich designed the interiors of all German industrial sections at the Barcelona International Exposition, where the Bauhaus sent objects from its carpentry, metal, and weaving workshops. Josef and Anni Albers traveled to see the exhibition and then went to meet Vassily Kandinsky and Paul Klee, who spent over a month on holiday in the Côte Basque. Albers captured their trip in photo collages, Kandinsky registered his impressions in snapshots, while Klee wrote abundant correspondence and produced drawings. Focusing on the itineraries the Bauhäusler followed, along with the means by which they expressed their travel impressions, this article reveals the effect of travel in their later design attitudes and work. Significant cultural transfers between Germany and Spain took place in a critical moment of European history, suggesting that further developments of these learning experiences might have materialized later on both sides of the border, possibly even reaching across the Atlantic.

  15. Patient perspectives on antipsychotic treatments and their association with clinical outcomes

    Directory of Open Access Journals (Sweden)

    Hong Liu-Seifert

    2010-09-01

    Full Text Available Hong Liu-Seifert1, Olawale O Osuntokun1, Jenna L Godfrey2, Peter D Feldman11Lilly Research Laboratories, Indianapolis, IN, USA; 2Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: This analysis examined patient-reported attitudes toward antipsychotic medication and the relationship of these attitudes with clinical outcomes and pharmacotherapy adherence. The analysis included three randomized, double-blind studies in patients with schizophrenia, schizoaffective disorder, or schizophreniform disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition and randomly assigned to treatment with olanzapine 5–20 mg/day or another antipsychotic (haloperidol 2–20 mg/day, risperidone 2–10 mg/day, or ziprasidone 80–160 mg/day. Patient-reported improvements were significantly greater for olanzapine (n = 488 versus other treatments (haloperidol n = 145, risperidone n = 158, or ziprasidone n = 271 on multiple Drug Attitude Inventory items. A positive attitude toward medication reported by patients was significantly associated with greater clinical improvement on the Positive and Negative Syndrome Scale and lower discontinuation rates. These results suggest that patients’ perceptions of treatment benefits are associated with objective clinical measures, including reduction of symptom severity and lower discontinuation rates. Furthermore, olanzapine may be associated with more positive treatment attitudes. These findings may contribute to a better understanding of reasons for treatment adherence from patients’ own perspectives.Keywords: antipsychotic agents, medication adherence, patient satisfaction, schizophrenia, treatment efficacy

  16. Indiana Wesleyan University SPS Physics Outreach to Rural Middle School and High School Students

    Science.gov (United States)

    Ostrander, Joshua; Rose, Heath; Burchell, Robert; Ramos, Roberto

    2013-03-01

    The Society of Physics Students chapter at Indiana Wesleyan University is unusual in that it has no physics major, only physics minors. Yet while just over a year old, IWU-SPS has been active in performing physics outreach to middle school and high school students, and the rural community of Grant County. Our year-old SPS chapter consists of majors from Chemistry, Nursing, Biology, Exercise Science, Computer Science, Psychology, Pastoral Studies, and Science Education, who share a common interest in physics and service to the community. IWU currently has a physics minor and is currently working to build a physics major program. Despite the intrinsic challenges, our multi-disciplinary group has been successful at using physics demonstration equipment and hands-on activities and their universal appeal to raise the interest in physics in Grant County. We report our experience, challenges, and successes with physics outreach. We describe in detail our two-pronged approach: raising the level of physics appreciation among the IWU student community and among pre-college students in a rural community of Indiana. Acknowledgements: We acknowledge the support of the Society of Physics Students through a Marsh White Outreach Award and a Blake Lilly Prize.

  17. The cluster environments of powerful radio-loud and radio-quiet AGN

    CERN Document Server

    McLure, R J

    2000-01-01

    The spatial clustering amplitude (B_{gq}) is determined for a sample of 44 powerful AGN at z~0.2. No significant difference is detected in the richness of the cluster environments of the radio-loud and radio-quiet sub-samples, both of which typically inhabit environments as rich as Abell Class ~0. Comparison with radio luminosity-matched samples from Hill & Lilly (1991) and Wold et al. (2000a) suggests that there is no epoch-dependent change in environment richness out to at least z>=0.5 for either radio galaxies or radio quasars. Comparison with the APM cluster survey shows that, contrary to current folklore, powerful AGN do not avoid rich clusters, but rather display a spread in cluster environment which is perfectly consistent with being drawn at random from the massive elliptical population. Finally, we argue that virtually all Abell class ~0 clusters contained an active galaxy during the epoch of peak quasar activity at z~2.5.

  18. Novel Phenotypic Outcomes Identified for a Public Collection of Approved Drugs from a Publicly Accessible Panel of Assays.

    Directory of Open Access Journals (Sweden)

    Jonathan A Lee

    Full Text Available Phenotypic assays have a proven track record for generating leads that become first-in-class therapies. Whole cell assays that inform on a phenotype or mechanism also possess great potential in drug repositioning studies by illuminating new activities for the existing pharmacopeia. The National Center for Advancing Translational Sciences (NCATS pharmaceutical collection (NPC is the largest reported collection of approved small molecule therapeutics that is available for screening in a high-throughput setting. Via a wide-ranging collaborative effort, this library was analyzed in the Open Innovation Drug Discovery (OIDD phenotypic assay modules publicly offered by Lilly. The results of these tests are publically available online at www.ncats.nih.gov/expertise/preclinical/pd2 and via the PubChem Database (https://pubchem.ncbi.nlm.nih.gov/ (AID 1117321. Phenotypic outcomes for numerous drugs were confirmed, including sulfonylureas as insulin secretagogues and the anti-angiogenesis actions of multikinase inhibitors sorafenib, axitinib and pazopanib. Several novel outcomes were also noted including the Wnt potentiating activities of rotenone and the antifolate class of drugs, and the anti-angiogenic activity of cetaben.

  19. The effect of federal and state off-label marketing investigations on drug prescribing: The case of olanzapine.

    Science.gov (United States)

    Wang, Bo; Studdert, David M; Sarpatwari, Ameet; Franklin, Jessica M; Landon, Joan; Kesselheim, Aaron S

    2017-01-01

    In the past decade, the federal government has frequently investigated and prosecuted pharmaceutical manufacturers for illegal promotion of drugs for indications not approved by the Food and Drug Administration (FDA) ("off-label" uses). State governments can choose to coordinate with the federal investigation, or pursue their own independent state investigations. One of the largest-ever off-label prosecutions relates to the atypical antipsychotic drug olanzapine (Zyprexa). In a series of settlements between 2008 and 2010, Eli Lilly paid $1.4 billion to the federal government and over $290 million to state governments. We examined the effect of these settlements on off-label prescribing of this medication, taking advantage of geographical differences in states' involvement in the investigations and the timing of the settlements. However, we did not find a reduction in off-label prescribing; rather, there were no prescribing changes among states that joined the federal investigation, those that pursued independent state investigations, and states that pursued no investigations at all. Since the settlements of state investigations of off-label prescribing do not appear to significantly impact prescribing rates, policymakers should consider alternate ways of reducing the prevalence of non-evidence-based off-label use to complement their ongoing investigations.

  20. Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories.

    Science.gov (United States)

    Kim, Kyuri; Chini, Naseem; Fairchild, David G; Engle, Steven K; Reagan, William J; Summers, Sandra D; Mirsalis, Jon C

    2016-12-01

    There is a great need for improved diagnostic and prognostic accuracy of potential cardiac toxicity in drug development. This study reports the evaluation of several commercially available biomarker kits by 3 institutions (SRI, Eli Lilly, and Pfizer) for the discrimination between myocardial degeneration/necrosis and cardiac hypertrophy as well as the assessment of the interlaboratory and interplatform variation in results. Serum concentrations of natriuretic peptides (N-terminal pro-atrial natriuretic peptide [NT-proANP] and N-terminal pro-brain natriuretic peptide [NT-proBNP]), cardiac and skeletal troponins (cTnI, cTnT, and sTnI), myosin light chain 3 (Myl3), and fatty acid binding protein 3 (FABP3) were assessed in rats treated with minoxidil (MNX) and isoproterenol (ISO). MNX caused increased heart-to-body weight ratios and prominent elevations in NT-proANP and NT-proBNP concentrations detected at 24-hr postdose without elevation in troponins, Myl3, or FABP3 and with no abnormal histopathological findings. ISO caused ventricular leukocyte infiltration, myocyte fibrosis, and necrosis with increased concentrations of the natriuretic peptides, cardiac troponins, and Myl3. These results reinforce the advantages of a multimarker strategy in elucidating the underlying cause of cardiac insult and detecting myocardial tissue damage at 24-hr posttreatment. The interlaboratory and interplatform comparison analyses also showed that the data obtained from different laboratories and platforms are highly correlated and reproducible, making these biomarkers widely applicable in preclinical studies.

  1. Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR(®)/ABASAGLAR(®)) approved in the European Union.

    Science.gov (United States)

    Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

    2017-08-01

    Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Short outlines of books by Estonian authors / Janika Kronberg, Rutt Hinrikus

    Index Scriptorium Estoniae

    Kronberg, Janika, 1963-

    2003-01-01

    Sinijärv, Karl- Martin. Artutart & 39. Tallinn : Tuum, 2002 ; Beier, Priidu. Monaco. Tartu : P. Beier, 2002 ; Malin, Jaan. Sulle. Tartu : J. Malin, 2003 ; Liiv, Toomas. Luuletused 1968-2002. Tallinn : Tuum, 2003 ; Mägi, Arvo. Katk ja koolera. Tartu : Ilmamaa ; Kross, Jaan. Omaeluloolisus ja alltekst. Tallinn : Eesti Keele Sihtasutus, 2003 ; Kaplinski, Jaan ; Salminen, Johannes. Ööd valged ja mustad. Tallinn : Loomingu Raamatukogu, 2003 ; Kauksi Ülle. Käänüpäiv. Tartu : Kauksi Ülle Mänedsment', 2003 ; Luik, Tõnu. Filosoofiast kõnelda. Tartu : Ilmamaa, 2002 ; Teder, Tarmo. Pööningujutud. Tallinn : Eesti Keele Sihtasutus, 2002 ; Vetemaa, Enn. Minu väga magus elu ehk martsipanimeister. Tallinn : Tänapäev, 2002 ; Põldroos, Enn. Joonik kivi. Tallinn : Eesti Keele Sihtasutus, 2003 ; Suburg, Lilli. Kogutud kirjatööd. Tallinn : Eesti Raamat, 2002 ; Mikelsaar, Henn. Müüritud. Tartu : Ilmamaa, 2003 ; Kaus, Jan. Õndsate tund. Tallinn : Tuum, c2003

  3. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  4. [New aspects of pancreatic beta cell functions and their possible therapeutic applications].

    Science.gov (United States)

    Tiedge, M

    2006-12-01

    Using the metabolic stimulus-secretion coupling of pancreatic beta cells as an example, this review illustrates how new strategies in the treatment of type 2 diabetes mellitus can be developed from the results of basic research. Metabolic stimulus-secretion coupling presupposes the metabolizing of those stimuli of insulin secretion that have the properties of nutritional substances. Changes in the ATP/ADP ratio within the beta cells will then trigger the release of insulin granules from them. Glucokinase, a glucose phosphorylating enzyme, functions as a metabolic glucose sensor, which couples changes in physiological glucose concentration in the pancreatic beta cells and in the liver to the intermediary metabolism, i.e. glycolysis, the citrate cycle and respiratory-chain phosphorylation. In this way insulin secretion and hepatic metabolism are positively influenced. Several pharmaceutical companies (Roche, Merck, Astra-Zeneca, Lilly) have recently developed first examples of glucokinase-activating compounds and demonstrated in animal models their efficacy in the treatment of type 2 diabetes mellitus. These glucokinase activators prevent glucokinase from changing into a catalytically inactive structure. They also increase glucose affinity of the enzyme and stabilize a catalytically active form of glucokinase proteins. In this way glucokinase activators increase glucose-induced insulin secretion and inhibit hepatic glucogenesis. Glucokinase activators are an interesting innovation in the future treatment of type 2 diabetes, because their action on beta cells and the liver is caused by changes in blood glucose concentration.

  5. AMCP Partnership Forum: Navigating Innovations in Diabetes Care.

    Science.gov (United States)

    2016-12-01

    New developments that provide opportunities to enhance cost-effective diabetes care include advances in the pharmacologic treatment of diabetes, new drug delivery devices, innovations in patient management strategies, contracting strategies that incentivize effective interventions, and mobile health technologies. Payers must carefully consider the utility of these advances when making coverage decisions and designing benefits. To engage national stakeholders in a discussion about how to utilize innovations in diabetes care to optimize patient outcomes, the Academy of Managed Care Pharmacy organized the Partnership Forum on Navigating Innovations in Diabetes Care in Arlington, Virginia, on July 19-20, 2016. The forum explored current trends and advances in diabetes treatments and engaged in discussions about how organizations can leverage these emerging options to develop strategies that improve coordination of care and patient outcomes, while managing limited health resources. Additionally, stakeholders were tasked with identifying gaps in evidence that hinder decision making around novel therapies and other advances that are of direct relevance to managed care organizations. The AMCP Partnership Forum on Navigating Innovations in Diabetes Care and the development of this proceedings document were supported by Boehringer Ingelheim, Lilly, Dexcom, Insulet Corporation, Intarcia Therapeutics, and Merck.

  6. Optimization Of Blasting Design Parameters On Open Pit Bench A Case Study Of Nchanga Open Pits

    Directory of Open Access Journals (Sweden)

    Victor Mwango Bowa

    2015-08-01

    Full Text Available Abstract In hard rock mining blasting is the most productive excavation technique applied to fragment insitu rock to the required size for efficient loading and crushing. In order to blast the insitu rock to the desired fragment size blast design parameter such as bench height hole diameter spacing burden hole length bottom charge specific charge and rock factor are considered. The research was carried out as a practical method on Nchanga Open Pits NOP ore Bench to optimize the blasting design parameters that can yield the required fragmentation size thereby reducing the shovel loading times and maximizing efficiency of the subsequent mining unit operations such as hauling and crushing. Fragmentation characteristics such as the mean fragment size were measured by means of a digital measuring tape and predicated using the Kuznetsov equation and rock factor value of ore bench was calculated using Lilly 1986 equations by means of rock characteristics. Traditional blasting design parameters were acquired for NOP and modified using Langerfors and Sharma P.A approaches. Several blast operations were conducted using both traditional and modified blasting design parameters on the same ore bench with the same geological conditions. Loading times of the shovel and fragment sizes were obtained after the blasts from ore bench where both the traditional and modified blasting design parameters were applied. Results show that mean fragment size and loading times were reduced from 51cm and 12minutes to 22cm and 3minutes where traditional and modified blasting design parameters were applied respectively.

  7. Benefits of switching from latanoprost to preservative-free tafluprost eye drops: a meta-analysis of two Phase IIIb clinical trials

    Directory of Open Access Journals (Sweden)

    Uusitalo H

    2016-03-01

    Full Text Available Hannu Uusitalo,1 Evgeniy Egorov,2 Kai Kaarniranta,3 Yuri Astakhov,4 Auli Ropo5 On behalf of the Switch Study Tafluprost Study Groups 1Department of Ophthalmology, SILK, University of Tampere, Tampere University Hospital, Tampere, Finland; 2Department of Ophthalmology, The Russian National Research Medical University, Moscow, Russia; 3Department of Ophthalmology, University of Eastern Finland, Kuopio University Hospital, Kuopio, Finland, 4Department of Ophthalmology, First Pavlov State Medical University of St Petersburg, Saint Petersburg, Russia, 5Global Medical Affairs, Santen Oy, Tampere, Finland Introduction: Glaucoma patients frequently exhibit ocular surface side effects during treatment with prostaglandin eye drops. The present work investigated whether glaucoma patients suffering from signs and symptoms of ocular surface disease while using preserved latanoprost eye drops benefited from switching to preservative-free tafluprost eye drops. Patients and methods: The analysis was based on 339 glaucoma patients enrolled in two Phase IIIb trials. The patients were required to have two symptoms, or one sign and one symptom of ocular surface disease at baseline, and at least 6 months preceding treatment with latanoprost eye drops preserved with benzalkonium chloride. All eligible patients were switched from latanoprost to preservative-free tafluprost for a total of 12 weeks. Ocular symptoms and ocular signs were evaluated at baseline and at 2 weeks, 6 weeks, and 12 weeks after commencing treatment with tafluprost. Intraocular pressure (IOP, drop discomfort, and treatment preference were evaluated to investigate the clinical efficacy and patient-related outcomes. Results: After 12 weeks of treatment with preservative-free tafluprost, the incidences of irritation/burning/stinging, foreign body sensation, tearing, itching, and dry eye sensation had diminished to one-third of those reported for preserved latanoprost at baseline. The incidences

  8. Health care resource use and direct medical costs for patients with schizophrenia in Tianjin, People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Wu J

    2015-04-01

    Full Text Available Jing Wu,1 Xiaoning He,1 Li Liu,2 Wenyu Ye,2 William Montgomery,3 Haibo Xue,2 Jeffery S McCombs41School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, People’s Republic of China; 2Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, People’s Republic of China; 3Eli Lilly and Company, Sydney, Australia; 4Departments of Clinical Pharmacy and Pharmaceutical Economics and Policy, School of Pharmacy, University of Southern California, Los Angeles, CA, USAObjective: Information concerning the treatment costs of schizophrenia is scarce in People’s Republic of China. The aims of this study were to quantify health care resource utilization and to estimate the direct medical costs for patients with schizophrenia in Tianjin, People’s Republic of China.Methods: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance (UEBMI database. Adult patients with ≥1 diagnosis of schizophrenia and 12-month continuous enrollment after the first schizophrenia diagnosis between 2008 and 2009 were included. Both schizophrenia-related, psychiatric-related, and all-cause related resource utilization and direct medical costs were estimated.Results: A total of 2,125 patients were included with a mean age of 52.3 years, and 50.7% of the patients were female. The annual mean all-cause costs were $2,863 per patient with psychiatric-related and schizophrenia-related costs accounting for 84.1% and 62.0% respectively. The schizophrenia-related costs for hospitalized patients were eleven times greater than that of patients who were not hospitalized. For schizophrenia-related health services, 60.8% of patients experienced at least one hospitalization with a mean (median length of stay of 112.1 (71 days and a mean cost of $1,904 per admission; 59.0% of patients experienced at least one outpatient visit with a mean (median number of visits of 6.2 (4 and a mean cost of $42 per visit during the 12-month follow-up period. Non

  9. Temporal Trends in Use of Biologic DMARDs for Rheumatoid Arthritis in the United States: A Cohort Study of Publicly and Privately Insured Patients.

    Science.gov (United States)

    Desai, Rishi J; Solomon, Daniel H; Jin, Yinzhu; Liu, Jun; Kim, Seoyoung C

    2017-08-01

    patients used bDMARDs in recent years, and use of newer agents, including certolizumab, golumumab, and tocilizuamab, is rising, which highlights a need for further comparative safety and effectiveness research of these agents to better guide evidence-based decision making. This study was supported by an investigator-initiated research grant from Pfizer. The study was conducted by the authors independent of the sponsor. The sponsor was given the opportunity to make nonbinding comments on a draft of the manuscript, but the authors retained the right of publication and determined the final wording. Solomon receives salary support through research support to his hospital from Amgen, Pfizer, AstraZeneca, Genentech, Lilly, Bristol-Myers Squibb, and CORRONA. Kim receives research grants from AstraZeneca, Lilly, Pfizer, Bristol-Myers Squibb, and Genentech. Desai receives research grants from Merck. Study concept and design were contributed by Desai and Kim. Liu took the lead in data collection, along with Jin, Desai, and Kim. All authors contributed equally in the interpretation of the results. The manuscript was written and revised primarily by Desai, along with Kim and the other authors.

  10. The risk of bleeding with duloxetine treatment in patients who use nonsteroidal anti-inflammatory drugs (NSAIDs: analysis of placebo-controlled trials and post-marketing adverse event reports

    Directory of Open Access Journals (Sweden)

    Perahia DG

    2013-11-01

    Full Text Available David G Perahia,1 Mark E Bangs,2 Qi Zhang,2 Yingkai Cheng,2 Jonna Ahl,2 Elijah P Frakes,2 Michael J Adams,2 James M Martinez2 1Neurosciences, Lilly Research Centre, Windlesham, Surrey, UK; 2Neurosciences, Eli Lilly and Company, Indianapolis, IN, USA Purpose: To assess the safety of duloxetine with regards to bleeding-related events in patients who concomitantly did, versus did not, use nonsteroidal anti-inflammatory drugs (NSAIDs, including aspirin. Methods: Safety data from all placebo-controlled trials of duloxetine conducted between December 1993 and December 2010, and post-marketing reports from duloxetine-treated patients in the US Food and Drug Administration Adverse Event Reporting System (FAERS, were searched for bleeding-related treatment-emergent adverse events (TEAEs. The percentage of patients with bleeding-related TEAEs was summarized and compared between treatment groups in all the placebo-controlled studies. Differences between NSAID user and non-user subgroups from clinical trial data were analyzed by a logistic regression model that included therapy, NSAID use, and therapy-by-NSAID subgroup interaction. In addition, to determine if higher duloxetine doses are associated with an increased incidence of bleeding-related TEAEs, and whether the use of concomitant NSAIDs might influence the dose effect if one exists, placebo-controlled clinical trials with duloxetine fixed doses of 60 mg, 120 mg, and placebo were analyzed. Also, the incidence of bleeding-related TEAEs reported for duloxetine alone was compared with the incidence in patients treated with duloxetine and concomitant NSAIDs. Finally, the number of bleeding-related cases reported for duloxetine in the FAERS database was compared with the numbers reported for all other drugs. Results: Across duloxetine clinical trials, there was a significantly greater incidence of bleeding-related TEAEs in duloxetine- versus placebo-treated patients overall and also in those patients who

  11. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Chen JH

    2016-04-01

    Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

  12. Medication use patterns, health care resource utilization, and economic burden for patients with major depressive disorder in Beijing, People’s Republic of China

    Directory of Open Access Journals (Sweden)

    Zhang L

    2016-04-01

    Full Text Available Ling Zhang,1–4 Yun Chen,5 Li Yue,5 Qingjing Liu,6 William Montgomery,7 Lihua Zhi,5 Wanqi Wang51Mood Disorders Center, Beijing Anding Hospital, Capital Medical University, 2China Clinical Research Center for Mental Disorders, 3China Center of Depression, Beijing Institute for Brain Disorders, 4Department of Psychiatry, Capital Medical University, Beijing, 5Medical Department, Lilly Suzhou Pharmaceutical Company, Ltd, Shanghai, 6Pharmacoeconomics and Outcomes Research, Beijing Brainpower Pharma Consulting Co, Ltd, Beijing, People’s Republic of China; 7Medical Department, Eli Lilly Australia Pty, Ltd, Sydney, NSW, AustraliaObjective: The objective of the study was to investigate medication usage patterns, health care resource utilization, and direct medical costs of patients with major depressive disorder (MDD in Beijing, People’s Republic of China.Methods: Data were extracted from a random sample of the Beijing Urban Employee Basic Medical Insurance database. Patients aged ≥18 years, with ≥1 primary diagnosis of MDD and 12-month continuous enrollment after their first observed MDD diagnosis between 2012 and 2013 were identified. Those with a diagnosis of schizophrenia, bipolar disorder, or cancer during the analysis period were excluded.Results: In total 8,484 patients, with mean age of 57.2 years, were included and 63% were female. The top three commonly observed comorbidities were hypertension (70.9%, anxiety disorder (68.6%, and coronary heart disease (65.1%. Furthermore, 71.4% of patients were treated with antidepressant medications, including 60.5% of patients treated with selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (9.0% and serotonin–norepinephrine reuptake inhibitors (8.3%. The proportions of patients who discontinued their initial antidepressant within the first and second months after the index date were 45.4% and 77.0%, respectively. Concomitant

  13. Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

    Directory of Open Access Journals (Sweden)

    Ampudia-Blasco FJ

    2017-01-01

    Full Text Available Francisco Javier Ampudia‑Blasco,1 Irene Romera,2 Bernat Ariño,3 Ramón Gomis4 1Endocrinology and Nutrition Department, Clinic University Hospital Valencia, Valencia, Spain; 2Eli Lilly and Company España, Madrid, Spain; 3Boehringer Ingelheim España, Barcelona, Spain; 4Endocrinology Department, Hospital Clinic Barcelona, Barcelona, Spain Background: The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2 inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text: Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion: There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin. Keywords: cardiovascular, outcome studies, SGLT2 inhibitors, empagliflozin, dapagliflozin, canagliflozin

  14. Photobiomodulation with Near Infrared Light Helmet in a Pilot, Placebo Controlled Clinical Trial in Dementia Patients Testing Memory and Cognition

    Science.gov (United States)

    Berman, Marvin H; Halper, James P; Nichols, Trent W; Jarrett, H; Lundy, Alan; Huang, Jason H

    2017-01-01

    Alzheimer’s disease (AD) is a common, chronic expensive debilitating neurodegenerative disease with no current treatments to prevent the physical deterioration of the brain and the consequent cognitive deficits. The current pathophysiology of Alzheimer’s disease is the accumulation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein and amyloid-beta (Aβ) plaques. Antibody therapy of Tau and Amyloid beta, vaccines and other methods to decrease Tau and or Amyloid have not been successful after considerable pharmaceutical and biotech efforts. For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer’s drug solanezumab which failed to reach statistical significance. Recently, a report on animal models using photomodulation with near infrared light to treat AD pathology in K369I tau transgenic model (K3) l engineered to develop neurofibrillary tangles, and the APPs/PSEN1dE9 transgenic model (APP/PS1) to develop amyloid plaques. Mice were treated with NIR 20 times over a four-week period and NIR treatment (600–1000 nm) was associated with a reduction in the size and number of amyloid-β plaques in the neocortex and hippocampus. We now report a small pilot double blind, placebo-controlled trial (n=11) 6 active, 3 controls and 2 dropouts assessing the effect of 28 consecutive, sixminute transcranial sessions of near infrared (NIR) stimulation using 1060–1080 nm light emitting diodes. Subjects were independently diagnosed with dementia conducted in an outpatient behavioral healthcare clinic. IRB approval was obtained through the Quietmind Foundation’s institutional review Board (IRB). Results showed changes in executive functioning; clock drawing, immediate recall, praxis memory, visual attention and task switching (Trails A&B) as well as a trend of improved EEG amplitude and connectivity measures. Neuroplasticity has also been reported with NIR light stimulation and mitochondrial enhancement. PMID

  15. Differential RNA expression between schizophrenic patients and controls of the dystrobrevin binding protein 1 and neuregulin 1 genes in immortalized lymphocytes.

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    Chagnon, Y C; Roy, M-A; Bureau, A; Mérette, C; Maziade, M

    2008-03-01

    The dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1) genes have been related to schizophrenia (SZ) and bipolar disorder (BP) by several whole-genome linkage and associations studies. Few expression studies in post-mortem brains have also reported a lower or a higher expression of DTNBP1 and NRG1, respectively, in SZ. Since the difficulty to access post-mortem brains, we evaluated RNA expression of DTNBP1 and NRG1 in immortalized lymphocytes of SZ patients and unrelated-family controls. An antipsychotic stimulation was also used to challenge the genetic background of the subjects and enhance differential expression. Immortalized lymphocytes of twelve SZ and twelve controls were grown individually in the presence or not of the antipsychotic olanzapine (Zyprexa; EliLilly). RNA was extracted and pooled in four groups of three SZ and four groups of three controls, and used to probe Agilent 18K microchips. Mean gene expression values were contrasted between SZ and control groups using a T-test. For DTNBP1, RNA expression was lower in SZ than in controls before (-28%; p=0.02) and after (-30%; p=0.01) olanzapine stimulation. Similarly, NRG1 GGF2 isoform showed a lower expression in SZ before (-29%; p=0.04) and after (-33%; p=0.02) olanzapine stimulation. In contrast, NRG1 GGF isoform showed no significant difference between SZ and controls (-7%; p=0.61, +3%; p=0.86, respectively), but was slightly repressed by olanzapine in controls (-8%; p=0.008) but not in SZ (+1%; p=0.91). These results are in agreement with those observed in post-mortem brain when the isoforms involved are considered.

  16. Assessing the effect of weight and weight loss in obese persons with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Bradley Curtis

    2008-10-01

    Full Text Available Bradley Curtis1, Risa P Hayes1, Sheri Fehnel2, Laurie Zografos21Global Health Outcomes, Eli Lilly and Co, Indianapolis, IN, USA; 2RTI Health Solutions, Research Triangle Park, NC, USAAbstract: The objective of this study was to assess specific areas of life in which obesity affects individuals with type 2 diabetes mellitus (T2DM, and changes that obese persons with T2DM experience with weight loss of varying degrees. Thirty in-depth interviews were conducted in persons identified as: age ≥40 years, diagnosed with T2DM for ≥2 years, on oral antihyperglycemic medications >3 months, BMI 30–35 kg/m2, having attempted to lose weight in the last 2 years. Participants (60% female, mean age 53 years, 53% Caucasian, mean BMI 32.2 kg/m2 agreed that 5% weight loss, while not reflective of an ultimate goal, would be meaningful and important; benefits were expected to accrue in physical functioning, self-confidence, blood glucose levels, and motivation to keep losing weight. Participants reported the greatest effect of weight loss on energy, physical activity, mobility, pain, and clothes/appearance. Participants reported weight affecting mood, with feelings of depression and frustration most commonly described. This research indicates that weight loss is likely to affect health-related quality of life in obese individuals with T2DM. Given the purported weight loss benefits of many emerging diabetic medications, it will be important to include measures of weight-related quality of life in future clinical trials of these agents.Keywords: health-related quality of life, obesity, type 2 diabetes, weight loss, patient-reported outcomes

  17. The color purple: from royalty to laboratory, with apologies to Malachowski.

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    Krafts, K P; Hempelmann, E; Oleksyn, B J

    2011-02-01

    The components of the blood stain, eosin and methylene blue, were introduced by Baeyer and Caro, respectively. Methylene blue was used primarily for detecting Mycobacterium tuberculosis until Ehrlich in 1880 mixed methylene blue with acid fuchsin to produce what he termed a "neutral stain," which allowed differentiation of blood cells. Eight years later, Chęciń ski changed the acidic component of the dye to eosin. Plehn subsequently altered the proportions of eosin and methylene blue to produce a greater range of red and blue hues. In 1891, Malachowski and Romanowsky independently developed stains composed of eosin and "ripened" methylene blue that not only differentiated blood cells, but also demonstrated the nuclei of malarial parasites. A number of "ripening" or "polychroming" techniques were investigated by different groups, but the aqueous dye solutions produced were unstable and precipitated rapidly. Subsequently, methanol was introduced as a solvent for the dye precipitate and techniques were developed that utilized the fixative properties of the methanolic solution prior to aqueous dilution for staining. This avoided the troublesome process of heat fixation of blood films. Giemsa further improved these techniques by using more controlled methods of methylene blue demethylation. In addition, he used measured amounts of known dyes and increased dye stability by adding glycerol to the methanol solvent. With the outbreak of World War I, it became difficult to obtain German dyes outside of Germany; during the World War II, it became impossible. In their effort to improve the inferior American versions of Giemsa's stain, Lillie, Roe, and Wilcox discovered that the best staining results were obtained using pure methylene blue, one of its breakdown products (azure B) and eosin. These three substituents remain the major components of the stain to this day.

  18. Use of select medications prior to duloxetine initiation among commercially-insured patients

    Directory of Open Access Journals (Sweden)

    Bernauer M

    2012-08-01

    Full Text Available Mark Bernauer,1 Ning Wu,2 Shih-Yin Chen,2 Xiaomei Peng,1 Luke Boulanger,2 Yang Zhao11Eli Lilly and Company, Indianapolis, IN, 2United BioSource Corporation, Lexington, MA, USABackground: The purpose of this study was to assess select medication utilization prior to duloxetine initiation among patients with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain associated with osteoarthritis or low back pain.Methods: Commercially insured duloxetine initiators between January 1, 2007 and March 31, 2010 were identified from a large US administrative claims database. Disease subgroups were constructed based on diagnosis from medical claims during the 12 months prior to duloxetine initiation. Prior use of antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs, and muscle relaxants was assessed during the 12-month preinitiation period.Results: This study identified 56,845 (2007, 44,838 (2008, and 65,840 (January 2009 to March 2010 duloxetine initiators. Among the 2009 initiators, utilization patterns were similar for patients with major depressive disorder and generalized anxiety disorder, with antidepressants being the most used (84% and 80%, respectively, followed by opioids (58% and 55%, respectively. Patients across pain-related conditions also had similar utilization patterns, with opioid use being the highest (76%–82%, followed by antidepressants (65%–72%. Use of other medication classes was common (29%–63% but less frequent, and over 50% of the patients used any antidepressants, 70% used any antidepressants or anticonvulsants, and 90% used any antidepressants, anticonvulsants, or opioids. Trends in the use of these select medications were similar between 2007 and 2009.Conclusion: Patients used several types of medications over the 12 months prior to initiating duloxetine across disease states, with antidepressants and opioids being the

  19. Developing a Commercial Air Ultrasonic Ceramic Transducer to Transdermal Insulin Delivery.

    Science.gov (United States)

    Jabbari, Nasrollah; Asghari, Mohammad Hossein; Ahmadian, Hassan; Mikaili, Peyman

    2015-01-01

    The application of low-frequency ultrasound for transdermal delivery of insulin is of particular public interest due to the increasing problem of diabetes. The purpose of this research was to develop an air ultrasonic ceramic transducer for transdermal insulin delivery and evaluate the possibility of applying a new portable and low-cost device for transdermal insulin delivery. Twenty-four rats were divided into four groups with six rats in each group: one control group and three experimental groups. Control group (C) did not receive any ultrasound exposure or insulin (untreated group). The second group (T1) was treated with subcutaneous insulin (Humulin(®) R, rDNA U-100, Eli Lilly and Co., Indianapolis, IN) injection (0.25 U/Kg). The third group (T2) topically received insulin, and the fourth group (T3) received insulin with ultrasound waves. All the rats were anesthetized by intraperitoneal injection of ketamin hydrochloride and xylazine hydrochloride. Blood samples were collected after anesthesia to obtain a baseline glucose level. Additional blood samples were taken every 15 min in the whole 90 min experiment. In order for comparison the changes in blood glucose levels" to " In order to compare the changes in blood glucose levels. The statistical multiple comparison (two-sided Tukey) test showed a significant difference between transdermal insulin delivery group (T2) and subcutaneous insulin injection group (T1) during 90 min experiment (P = 0.018). In addition, the difference between transdermal insulin delivery group (T2) and ultrasonic transdermal insulin delivery group (T3) was significant (P = 0.001). Results of this study demonstrated that the produced low-frequency ultrasound from this device enhanced the transdermal delivery of insulin across hairless rat skin.

  20. Joint-constraint model for large-eddy simulation of helical turbulence.

    Science.gov (United States)

    Yu, Changping; Xiao, Zuoli; Shi, Yipeng; Chen, Shiyi

    2014-04-01

    A three-term mixed subgrid-scale (SGS) stress model is proposed for large-eddy simulation (LES) of helical turbulence. The new model includes a Smagorinsky-Lilly term, a velocity gradient term, and a symmetric vorticity gradient term. The model coefficients are determined by minimizing the mean square error between the realistic and modeled Leonard stresses under a joint constraint of kinetic energy and helicity fluxes. The model formulated as such is referred to as joint-constraint dynamic three-term model (JCD3TM). First, the new model is evaluated a priori using the direct numerical simulation (DNS) data of homogeneous isotropic turbulence with helical forcing. It is shown that the SGS dissipation fractions from all three terms in JCD3TM have the properties of length-scale invariance in inertial subrange. JCD3TM can predict the SGS stresses, energy flux, and helicity flux more accurately than the dynamic Smagorinsky model (DSM) and dynamic mixed helical model (DMHM) in both pointwise and statistical senses. Then, the performance of JCD3TM is tested a posteriori in LESs of both forced and freely decaying helical isotropic turbulence. It is found that JCD3TM possesses certain features of superiority over the other two models in predicting the energy spectrum, helicity spectrum, high-order statistics, etc. It is also noteworthy that JCD3TM is capable of simulating the evolutions of both energy and helicity spectra more precisely than other models in decaying helical turbulence. We claim that the present SGS model can capture the main helical features of turbulent motions and may serve as a useful tool for LES of helical turbulent flows.

  1. Evidence for accumulation of Synechococcus elongatus (Cyanobacteria: Cyanophyceae) in the tissues of the oyster Crassostrea gigas (Mollusca: Bivalvia).

    Science.gov (United States)

    Avila-Poveda, Omar Hernando; Torres-Ariño, Alejandra; Girón-Cruz, Diego Ademir; Cuevas-Aguirre, Angel

    2014-10-01

    Cyanobacteria appear to have direct relations with mollusks in several aspects. This is the first time, distinguishing Gram-negative cyanoprokaryotic Synechococcus elongatus as bright yellow-gold autofluorescence by Lillie's and Hiss' staining methods on paraffin-embedded tissues of Crassostrea gigas. Three diets: cyanoprokaryotes, cyanoprokaryotes with microalgae, and only microalgae were evaluated. Cyanoprokaryotes were intact, densely bundled, and immersed in the cytosol of the digestive gland, connective tissue, mantle, and gonad of C. gigas, revealing an accumulation systemic without tissue damage observed by histology. Unexpectedly, cyanoprokaryotes were slightly most accumulated with microalgae diet by each of the tissues of the C. gigas than with any other diets. Cyanoprokaryotes tend to be in mean slightly higher in the digestive gland than in any other tissues respectively for each diet, although these values are closely similar to connective tissue. A possible order of exposure of the oyster tissues to accumulation of cyanoprokaryotes was digestive gland, connective tissue, mantle, and gonad. Thereby, the digestive gland could be the major target tissue for the accumulation. Our observations provide a valuable insight regarding the ability of cyanoprokaryotes to penetrate, spread, and remain inside the oyster tissues, suggesting for S. elongatus: (1) a pre-accumulation in oyster tissues from the natural environment, (2) a phagocytosis and/or endocytosis process rather than ingestion and extracellular digestion, (3) an apparent cellular division in the cytosol of oyster tissues, (4) an apparent inter-tissue movement, and (5) a possible endosymbiosis between C. gigas and S. elongatus. Hereby, it is possible that S. elongatus have a well-developed host-endobiont relationship with oysters, and thereby support future work toward a description of the escape and spreading mechanisms of S. elongatus inside the tissues of mollusks, and put forward questions as

  2. Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures: Incidence of Ischemic and Hemorrhagic Complications.

    Science.gov (United States)

    Nordeen, Jerah D; Patel, Alden V; Darracott, Robert M; Johns, Gretchen S; Taussky, Philipp; Tawk, Rabih G; Miller, David A; Freeman, William D; Hanel, Ricardo A

    2013-06-01

    The purpose of the study was to assess clopidogrel resistance and whether "intensified" antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (Pharmaceuticals, Princeton, NJ, USA) VerifyNow® (Accumetrics Inc., San Diego, CA, USA) Ticlopidine (Ticlid®) (Roche Laboratories, Basel, Switzerland) Prasugrel (Effient®) (Eli Lilly & Co., Indianapolis, IN, USA) Eptifibatide (Integrilin®) (Merck & Co., Inc., Whitehouse Station, NJ, USA) Abciximab (Reopro®) (Janssen Pharmaceuticals, Inc., Titusville, NJ, USA) Tirofiban (Aggrastat®) (MGI Pharma, Inc., Bloomington, MN, USA) Pantoprazole (Protonix®) (Pfizer Inc., New York, NY, USA) Omeprazole (Prilosec®) (Procter and Gamble Pharmaceuticals, Mason, OH, USA) Famotidine (Pepcid®) (McNeil Consumer & Specialty Pharmaceuticals, Fort Washington, PA, USA) Ticagrelor (Brilinta®) (AstraZeneca Pharmaceuticals, Wilmington, NC, USA).

  3. Variability in P-Glycoprotein Inhibitory Potency (IC50) Using Various in Vitro Experimental Systems: Implications for Universal Digoxin Drug-Drug Interaction Risk Assessment Decision Criteria

    Science.gov (United States)

    Bentz, Joe; O’Connor, Michael P.; Bednarczyk, Dallas; Coleman, JoAnn; Lee, Caroline; Palm, Johan; Pak, Y. Anne; Perloff, Elke S.; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K.; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E.; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M.; Xia, Cindy Q.; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei

    2013-01-01

    A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells—Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC50 values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC50 values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC50 values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC50 values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC50 values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC50 determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens et al., 2013) and recommendations

  4. Stereological Changes of Human Placenta in Systemic Lupus Erythematosus Compared with Healthy Controls

    Directory of Open Access Journals (Sweden)

    Zahra Heidari

    2013-07-01

    Full Text Available Background: Systemic lupus erythematosus (SLE is a chronic autoimmune disease that can cause changes in the placenta. In this study, quantitative changes of placenta were investigated using stereological methods.Materials and Methods: In this case-control study, 10 placentas from systemic lupus erythematosus pregnancy (antinuclear antibody>10, and 10 placentas from normal uncomplicated pregnancy were obtained from Imam Ali Hospital. Volume of placentas was estimated using Cavalieri's principle. 3 full-thickness columns of each placenta were taken using systematic uniform random sampling (SURS. After fixation in modified Lillie's solution, they were cut into 5 mm slices. 5-7 sections selected from each slice using SURS and stained by Masson’s trichrome. Then stereological analyses were done on 8-10 SURS fields of each section. Placental volume, absolute volume and volume density of chorionic villi, intervillous space, syncytiotrophoblast, fibrin and blood vessels in chorionic villi were estimated in both groups. The Mann Whitney-U test was employed to determine statistically significant differences between the means. Significant level was set at p<0.05.Results: Total volume and volume density of fibrin and total volume and volume density of blood vessels significantly increased in SLE group in comparison with control group (p<0.01. Volume density of syncytiotrophoblast increased 50% in SLE group in comparison with control group, this increase was statistically significant (p<0.01.Conclusion: Results showed that systemic lupus erythematosus disease can cause significant changes in the structure of placenta that may be influential on the evolution and survival of fetus.

  5. Reducing employee exposure potential using the ANSI/ASHRAE 110 Method of Testing Performance of Laboratory Fume Hoods as a diagnostic tool.

    Science.gov (United States)

    Maupins, K; Hitchings, D T

    1998-02-01

    The primary goal of a laboratory ventilation system is to assure that employee exposure to hazardous chemicals does not exceed acceptable levels. Industrial hygienists at Eli Lilly & Co. were concerned about the adequacy of fume hoods to protect workers in an aging laboratory facility. Wanting to conduct a comprehensive series of tests for a true reading on the containment effectiveness of these hoods, the industrial hygienists went beyond the traditional face velocity tests. Tests prescribed in the ANSI/ASHRAE 110 Method of Testing Performance of Laboratory Fume Hoods (ASHRAE 110) standard including low- and high-volume smoke tests, face velocity tests, and tracer gas containment tests indicated that many of the hoods did not meet industry consensus standards for containment (0.1 ppm), yet met industry recommended face velocity specifications (80-120 ft/min). Based on the results of performance tests and engineering observations of the facility, apparent causes of poor performance were identified, and a mitigation plan was implemented to bring the hoods to the desired containment standards. After completion of the improvements, retesting was conducted to confirm achievement of these standards. Pre- and postmitigation test results, indicating a 99.5% reduction in tracer gas leakage or potential employee exposures, build a strong case for a more complete testing protocol as specified by the ASHRAE 110 test method. The authors recommend that traditional face velocity testing alone be discontinued in favor of the ASHRAE 110 method as a quantitative measure of fume hood performance coupled with the traditional face velocity measurement at periodic intervals to assure continued performance.

  6. Focus on olanzapine.

    Science.gov (United States)

    Green, B

    1999-01-01

    Olanzapine (2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5] benzodiazepine) is a novel antipsychotic agent of the theinobenzodiazepine class developed by Eli Lilly & Co. It has a pleotrophic pharmacology and affects the dopaminergic, serotonergic, muscarinic and adrenergic systems. The therapeutic advantage of recent antipsychotics (so-called atypical antipsychotics) has been attributed to additional serotonergic effects. Clinical studies and trials suggest that olanzapine is comparable or superior to haloperidol and may be superior to risperidone in terms of efficacy and side-effect profiles. The starting dose of olanzapine is a single dose of 10 mg. The drug reaches peak plasma levels in 5-8 h, and has a half-life of about 35 h, depending on metabolism. The recommended maximum dose is 20 mg daily, but higher doses have been employed. Abnormalities of the QTc interval on ECG are unlikely to occur and so there is no need for a baseline ECG as with sertindole, which has recently been withdrawn. The most common side-effects are somnolence and weight gain. About 40% of patients in clinical trials gain weight--especially if they are on a high starting dose and if they were underweight pre-treatment. Reported evidence to date suggests that olanzapine is relatively less likely to produce sexual dysfunction. In general, weight gain and sexual dysfunction are of great concern to people taking antipsychotics and the side-effect profile of any antipsychotic may affect compliance. Olanzapine's general efficacy and side-effect profile suggest that, unforeseen post-marketing complications notwithstanding, olanzapine deserves a major place in the first-line management of psychotic disorders.

  7. A breakthrough in enzyme technology to fight penicillin resistance-industrial application of penicillin amidase.

    Science.gov (United States)

    Buchholz, Klaus

    2016-05-01

    Enzymatic penicillin hydrolysis by penicillin amidase (also penicillin acylase, PA) represents a Landmark: the first industrially and economically highly important process using an immobilized biocatalyst. Resistance of infective bacteria to antibiotics had become a major topic of research and industrial activities. Solutions to this problem, the antibiotics resistance of infective microorganisms, required the search for new antibiotics, but also the development of derivatives, notably penicillin derivatives, that overcame resistance. An obvious route was to hydrolyse penicillin to 6-aminopenicillanic acid (6-APA), as a first step, for the introduction via chemical synthesis of various different side chains. Hydrolysis via chemical reaction sequences was tedious requiring large amounts of toxic chemicals, and they were cost intensive. Enzymatic hydrolysis using penicillin amidase represented a much more elegant route. The basis for such a solution was the development of techniques for enzyme immobilization, a highly difficult task with respect to industrial application. Two pioneer groups started to develop solutions to this problem in the late 1960s and 1970s: that of Günter Schmidt-Kastner at Bayer AG (Germany) and that of Malcolm Lilly of Imperial College London. Here, one example of this development, that at Bayer, will be presented in more detail since it illustrates well the achievement of a solution to the problems of industrial application of enzymatic processes, notably development of an immobilization method for penicillin amidase suitable for scale up to application in industrial reactors under economic conditions. A range of bottlenecks and technical problems of large-scale application had to be overcome. Data giving an inside view of this pioneer achievement in the early phase of the new field of biocatalysis are presented. The development finally resulted in a highly innovative and commercially important enzymatic process to produce 6-APA that

  8. Topical oxygen wound therapies for chronic wounds: a review.

    Science.gov (United States)

    Dissemond, J; Kröger, K; Storck, M; Risse, A; Engels, P

    2015-02-01

    Chronic wounds are an increasing problem in our ageing population and can arise in many different ways. Over the past decades it has become evident that sufficient oxygen supply is an essential factor of appropriate wound healing. Sustained oxygen deficit has a detrimental impact on wound healing, especially for patients with chronic wounds. This has been proven for wounds associated with peripheral arterial occlusive disease (PAOD) and diabetic foot ulcers (particularly in combination with PAOD). However, this is still under debate for other primary diseases. In the past few years several different new therapeutic approaches for topical oxygen therapies have been developed to support wound healing. These tend to fall into one of four categories: (1) delivery of pure oxygen either under pressurised or (2) ambient condition, (3) chemical release of oxygen via an enzymatic reaction or (4) increase of oxygen by facilitated diffusion using oxygen binding and releasing molecules. In this review article, the available therapeutic topical oxygen-delivering approaches and their impact on wound healing are presented and critically discussed. A summary of clinical data, daily treatment recommendations and practicability is provided. J. Dissemond received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: 3M, B. Braun, BSN, Coloplast, Convatec, Draco, Hartmann, KCI, Lohmann&Rauscher, Medoderm, Merz, Sastomed, Systagenix, UCB-Pharma, Urgo. K. Kröger received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: Bayer, Sanofi, GSK, Hartmann, Sastomed, UCB-Pharma, Urgo. M. Storck received an honorarium for lectures for the following companies: KCI, Systagenix, and UCB-Pharma. A. Risse received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: Bracco, Coloplast, Draco, Lilly Deutschland, NovoNordisk, Sastomed, Urgo. P. Engels received an

  9. Personality traits in adults with attention-deficit hyperactivity disorder and their unaffected first-degree relatives.

    Science.gov (United States)

    Pironti, Valentino Antonio; Lai, Meng-Chuan; Müller, Ulrich; Bullmore, Edward Thomas; Sahakian, Barbara Jacquelyn

    2016-07-01

    Attention-deficit hyperactivity disorder (ADHD) shows clear, albeit heterogeneous, cognitive dysfunctions. However, personality traits are not well understood in adults with ADHD, and it is unclear whether they are predisposing factors or phenotypical facets of the condition. To assess whether personality traits of impulsivity, sensation seeking and sensitivity to punishment and reward are predisposing factors for ADHD or aspects of the clinical phenotype. Twenty adults with ADHD, 20 unaffected first-degree relatives and 20 controls completed rating scales assessing traits of impulsivity, sensation seeking and sensitivity to punishment/reward. Compared with relatives and controls, individuals with ADHD showed increased impulsive personality traits, were more susceptible to boredom and presented hypersensitivity to reward but normal sensitivity to punishment. High impulsivity traits, heightened sensitivity to reward and boredom are associated with the phenotype of ADHD, rather than being predisposing factors, as these traits were not shared between ADHD probands and their relatives. E.T.B. is employed part-time by GSK and part-time by the University of Cambridge; he holds stock in GSK. B.J.S. consults for Cambridge Cognition, Servier and Lundbeck; she holds a grant from Janssen/J&J. U.M. has received honoraria for consultancy and speaking at conferences and travel expenses from Bristol-Myers Squibb, Eli Lilly, Janssen-Cilag, Lundbeck, Pharmacia-Upjohn and UCB Pharma. © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  10. Potential anticancer properties of bioactive compounds of Gymnema sylvestre and its biofunctionalized silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Arunachalam KD

    2014-12-01

    Full Text Available Kantha Deivi Arunachalam,1 Lilly Baptista Arun,1 Sathesh Kumar Annamalai,1 Aarrthy M Arunachalam2 1Center for Environmental Nuclear Research, SRM University, Potheri, Tamil Nadu, India; 2Division of Educational Services, Kaplan University (Medical, Washington DC, USA Background: Gymnema sylvestre is an ethno-pharmacologically important medicinal plant used in many polyherbal formulations for its potential health benefits. Silver nanoparticles (SNPs were biofunctionalized using aqueous leaf extracts of G. sylvestre. The anticancer properties of the bioactive compounds and the biofunctionalized SNPs were compared using the HT29 human adenoma colon cancer cell line.Methods: The preliminary phytochemical screening for bioactive compounds from aqueous extracts revealed the presence of alkaloids, triterpenes, flavonoids, steroids, and saponins. Biofunctionalized SNPs were synthesized using silver nitrate and characterized by ultraviolet–visible spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis, Fourier transform infrared spectroscopy, and X-ray diffraction for size and shape. The characterized biofunctionalized G. sylvestre were tested for its in vitro anticancer activity against HT29 human colon adenocarcinoma cells.Results: The biofunctionlized G. sylvestre SNPs showed the surface plasmon resonance band at 430 nm. The scanning electron microscopy images showed the presence of spherical nanoparticles of various sizes, which were further determined using the Scherrer equation. In vitro cytotoxic activity of the biofunctionalized green-synthesized SNPs (GSNPs indicated that the sensitivity of HT29 human colon adenocarcinoma cells for cytotoxic drugs is higher than that of Vero cell line for the same cytotoxic agents and also higher than the bioactive compound of the aqueous extract.Conclusion: Our results show that the anticancer properties of the bioactive compounds of G. sylvestre can be enhanced through

  11. Triplet transitions of neutral CO in the spectra of comets and the abundance of CO/sub 2/ or molecules containing the CO group in comets

    Energy Technology Data Exchange (ETDEWEB)

    Biermann, L.

    1976-03-01

    The high-dispersion spectra of comet Mrkos (1957 V) taken at Mt. Palomar by J. L. Greenstein and remeasured by A. Woszczyk contain many unidentified weak lines. The possibility that some of these lines belong to transitions between triplet levels of neutral CO molecules is investigated. Their presence would suggest excitation related to the dissociative recombination of a parent containing the CO group, which is first ionized by solar uv. Of 31 CO lines (of the Asundi and Triplet systems), 14 are masked by known or by questionably identified lines as statistically expected. Of the remaining 17, 13 coincide within a few tenths of an Angstrom with an unidentified line and 4 do not. These results are contrary to statistical expectations. (Some members of the third positive system of CO, which might be present, have not been included in the figures.) Although these figures strongly favor the identification proposed, the numbers are not large enough to support entirely the argument of a small statistical probability (0.2 percent) of the observed state. Also, the rotational structure of the CO bands for the triplet systems needs further investigation. C. F. Lillie's observations of comet Bennett (1970 II) between 1200 and 1800 A, especially of the fourth positive system of CO, seem to favor a cometary atmosphere characterized by a large relative abundance of CO/sub 2/ and/or molecules containing the CO group. A model outlined for comet Bennett at 0.8 a.u. seems to be approximately consistent with observations. The chemical aspects, however, especially need further consideration. New observations, particularly of the Cameron bands of CO, are needed to settle the questions raised.

  12. Albiglutide: Is a better hope against diabetes mellitus?

    Science.gov (United States)

    Sharma, Arun K; Thanikachalam, Punniyakoti V; Rajput, Satyendra K

    2016-02-01

    Type-2 diabetes mellitus (T2DM) is the chronic metabolic disorder which provokes several pitfall signalling. Though, a series of anti-diabetic drugs are available in the market but T2DM is still a huge burden on the developed and developing countries. Numerous studies and survey predict the associated baleful circumstances in near future due to incessant increase in this insidious disorder. The novelty of recent explored anti-diabetic drugs including glitazone, glitazaar and gliflozines seems to be vanished due to their associated toxic side effects. Brown and Dryburgh (1970) isolated an intestinal amino acid known as gastric inhibitory peptide (GIP) which had insulinotropic activity. Subsequently in 1985, another incretin glucagon likes peptide 1 (GLP-1) having potent insulinotropic properties was discovered by Schmidt and his co-workers. On the basis of results' obtained by Phase III Harmony program FDA approved (14 April, 2014) new GLP-1 agonist 'Albiglutide (ALB)', in addition to exiting components Exenatide (Eli Lilly, 2005) and Liraglutide (Novo Nordisk, 2010). ALB stimulates the release of protein kinase A (PKA) via different mechanisms which ultimately leads to increase in intracellular Ca(2+) levels. This increased intracellular Ca(2+) releases insulin vesicle from β-cells. In-addition, ALB being resistant to degradation by dipeptidyl peptidase-4 (DPP-4) and has longer half life. DPP-4 can significantly degrade the level of GLP-1 agonist by hydrolysis. In spite of potent anti-hypergycemic activity, ALB has pleiotropic action of improving cardiovascular physiology. In light of these viewpoints we reveal the individual pharmacological profile of ALB and the critical analyse about its future perspective in present review. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  13. 填充烧结铜球的T型管中流体混合的大涡模拟%LES of Fluid Mixing in a Tee With a Sintered Porous Medium

    Institute of Scientific and Technical Information of China (English)

    王永伟; 卢涛; 姜培学; 成鹏飞; 王奎升

    2012-01-01

    在FLUENT软件平台上,运用大涡模拟湍流模型及Smagorinsky-Lilly亚格子尺度模型,对填充有烧结铜球多孔介质的T型管道内冷热流体混合过程的流动与传热情况进行了数值计算,与未填充多孔介质时混合区域内的平均温度和温度波动、平均速度和速度波动等数据进行了对比,并对温度波动进行了功率谱密度分析.数值结果表明,多孔介质可有效削弱T型通道流体混合区域内的温度和速度波动,有效降低1 Hz至10 Hz频域中的温度波动的功率谱密度.%Mixing processes of hot and cold fluids in a tee with and without sintered copper spheres were simulated by FLUENT using the large-eddy simulation (LES) turbulent flow model and the sub-grid scale (SGS) Smagorinsky-Lilly ( SL) model with buoyancy. Comparisons of the numerical results of the two cases with and without sintered copper spheres show that the porous medium significantly reduces the velocity and temperature fluctuations, because the porous medium can effectively restrict the fluid flow and enhance heat transfer. The porous media obviously increase the pressure drop in the main duct. The porous medium reduces the PSD of the temperature fluctuations in the frequency range from 1 Hz to 10 Hz.

  14. Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J).

    Science.gov (United States)

    Saeki, Hidehisa; Nakagawa, Hidemi; Nakajo, Ko; Ishii, Taeko; Morisaki, Yoji; Aoki, Takehiro; Cameron, Gregory S; Osuntokun, Olawale O

    2017-04-01

    Psoriasis, a chronic, immune-mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open-label study was to evaluate the long-term efficacy and safety of ixekizumab, a humanized, anti-interleukin-17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment-emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52-week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis. © 2016 Eli Lilly Japan K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

  15. Cost Analyses in the US and Japan: A Cross-Country Comparative Analysis Applied to the PRONOUNCE Trial in Non-Squamous Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Hess, Lisa M; Rajan, Narayan; Winfree, Katherine; Davey, Peter; Ball, Mark; Knox, Hediyyih; Graham, Christopher

    2015-12-01

    Health technology assessment is not required for regulatory submission or approval in either the United States (US) or Japan. This study was designed as a cross-country evaluation of cost analyses conducted in the US and Japan based on the PRONOUNCE phase III lung cancer trial, which compared pemetrexed plus carboplatin followed by pemetrexed (PemC) versus paclitaxel plus carboplatin plus bevacizumab followed by bevacizumab (PCB). Two cost analyses were conducted in accordance with International Society For Pharmacoeconomics and Outcomes Research good research practice standards. Costs were obtained based on local pricing structures; outcomes were considered equivalent based on the PRONOUNCE trial results. Other inputs were included from the trial data (e.g., toxicity rates) or from local practice sources (e.g., toxicity management). The models were compared across key input and transferability factors. Despite differences in local input data, both models demonstrated a similar direction, with the cost of PemC being consistently lower than the cost of PCB. The variation in individual input parameters did affect some of the specific categories, such as toxicity, and impacted sensitivity analyses, with the cost differential between comparators being greater in Japan than in the US. When economic models are based on clinical trial data, many inputs and outcomes are held consistent. The alterable inputs were not in and of themselves large enough to significantly impact the results between countries, which were directionally consistent with greater variation seen in sensitivity analyses. The factors that vary across jurisdictions, even when minor, can have an impact on trial-based economic analyses. Eli Lilly and Company.

  16. Determination of Narasin in Chicken Fat: A Bridging Study Comparing the Bioautographic Method (FSIS CLG Method R22) to a Liquid Chromatography with Tandem Mass Spectrometry Method (AOAC Method 2011.24).

    Science.gov (United States)

    Mizinga, Kemmy M; Burnett, Thomas J; Brunelle, Sharon L; Wallace, Michael A; Coleman, Mark R

    2016-01-01

    Lilly Method AM-AA-CA-R108-AB-755, which is substantially the same as U.S. Department of Agriculture, Food Safety and Inspection Service (FSIS) Chemistry Laboratory Guidebook (CLG) method R22, is the current regulatory method for determining narasin in cattle and chicken tissues and is based on bioautography, creating a zone of inhibition of bacterial growth, with the size of the zone correlating to the amount of narasin extracted from the tissue. AOAC Method 2011.24 is an LC-tandem mass spectrometry (MS/MS) method for determining narasin content from bovine, swine, or chicken tissues. It has many advantages over the regulatory method, including higher throughput, less solvent use, no use of carbon tetrachloride, a wider method range, inclusion of swine tissues, and it is less labor intensive. In this study, AOAC Method 2011.24 was compared to FSIS CLG method R22 for the determination of narasin in chicken abdominal fat. Fortified chicken-fat samples ranging from 20 to 960 ng/g and incurred chicken-fat samples ranging from 40 to 480 ng/g were assayed by both methods in triplicate. Mean accuracies for the two methods were similar, 77-110% for CLG R22 and 84-96% for AOAC Method 2011.24, and the method results showed a linear correlation. The methods differed in precision, however, with the CLG R22 method yielding 2.6-34% RSD and AOAC Method 2011.24 yielding 0.15-6.4% RSD. It is recommended that AOAC Method 2011.24-granted AOAC Official Method(SM) Final Action status-be adopted as the official U.S. regulatory method.

  17. Twenty-first century learning in school systems: the case of the Metropolitan School District of Lawrence Township, Indianapolis, Indiana.

    Science.gov (United States)

    Capuano, Marcia; Knoderer, Troy

    2006-01-01

    To empower students with skills such as information and technological literacy, global awareness and cultural competence, self-direction, and sound reasoning, teachers must master these skills themselves. This chapter examines how the Digital Age Literacy Initiative of the Metropolitan School District of Lawrence Township in Indianapolis, Indiana, which is funded by the Lilly Endowment, incorporated twenty-first century learning through a systemic approach involving teacher training and the use of data. The authors explain the district's content, process, and context goals toward accomplishing its mission of empowering students with the necessary twenty-first century skills to succeed in the digital age. The district places a strong emphasis on professional development for teachers. To support the necessary teacher learning and therefore sustain the work of the initiative, the district has adopted action research, self-assessment, and an online professional development network. To support teachers in implementing new strategies, master teachers serve as digital age literacy coaches. The chapter discusses the initiative's focus on evidence of progress. Through a partnership with the Metiri Group of California, the district has built a range of assessments including online inventories and twenty-first century skill rubrics. For example, the Mankato Survey collected teacher and student data around access, ability, and use of technology in the classroom in 2001 and then in 2004. This research showed significant gains in some technologies across all grade levels and consistent gains in nearly all technologies for middle and high school students. As it moves into the next phase of implementing the Digital Age Literacy Initiative, the district embraces the systemic shifts in school culture necessary to institutionalize twenty-first century learning.

  18. The Mass-Metallicity and Fundamental Metallicity Relations at z > 2 Using Very Large Telescope and Subaru Near-infrared Spectroscopy of zCOSMOS Galaxies

    Science.gov (United States)

    Maier, C.; Lilly, S. J.; Ziegler, B. L.; Contini, T.; Pérez Montero, E.; Peng, Y.; Balestra, I.

    2014-09-01

    In the local universe, there is good evidence that, at a given stellar mass M, the gas-phase metallicity Z is anti-correlated with the star formation rate (SFR) of the galaxies. It has also been claimed that the resulting Z(M, SFR) relation is invariant with redshift—the so-called "fundamental metallicity relation" (FMR). Given a number of difficulties in determining metallicities, especially at higher redshifts, the form of the Z(M, SFR) relation and whether it is really independent of redshift is still very controversial. To explore this issue at z > 2, we used VLT-SINFONI and Subaru-MOIRCS near-infrared spectroscopy of 20 zCOSMOS-deep galaxies at 2.1 extinction corrected Hα measurements. We find that the mass-metallicity relation (MZR) of these star-forming galaxies at z ≈ 2.3 is lower than the local Sloan Digital Sky Survey (SDSS) MZR by a factor of three to five, a larger change than found by Erb et al. using [N II]/Hα-based metallicities from stacked spectra. We discuss how the different selections of the samples and metallicity calibrations used may be responsible for this discrepancy. The galaxies show direct evidence that the SFR is still a second parameter in the MZR at these redshifts. However, determining whether the Z(M, SFR) relation is invariant with epoch depends on the choice of extrapolation used from local samples, because z > 2 galaxies of a given mass have much higher SFRs than the local SDSS galaxies. We find that the zCOSMOS galaxies are consistent with a non-evolving FMR if we use the physically motivated formulation of the Z(M, SFR) relation from Lilly et al., but not if we use the empirical formulation of Mannucci et al. AND SUBARU

  19. Cultural Conditions for Mycelial Growth and Molecular Phylogenetic Relationship in Different Wild Strains of Schizophyllum commune.

    Science.gov (United States)

    Alam, Nuhu; Cha, Youn Jeong; Shim, Mi Ja; Lee, Tae Soo; Lee, U Youn

    2010-03-01

    The common split-gilled mushroom, Schizophyllum commune is found throughout the world on woody plants. This study was initiated to evaluate conditions for favorable vegetative growth and to determine molecular phylogenetic relationship in twelve different strains of S. commune. A suitable temperature for mycelial growth was obtained at 30℃. This mushroom grew well in acidic conditions and pH 5 was the most favorable. Hamada, glucose peptone, Hennerberg, potato dextrose agar and yeast malt extract were favorable media for growing mycelia, while Lilly and glucose tryptone were unfavorable. Dextrin was the best and lactose was the less effective carbon source. The most suitable nitrogen sources were calcium nitrate, glycine, and potassium nitrate, whereas ammonium phosphate and histidine were the least effective for the mycelial growth of S. commune. The genetic diversity of each strain was investigated in order to identify them. The internal transcribed spacer (ITS) regions of rDNA were amplified using PCR. The size of the ITS1 and ITS2 regions of rDNA from the different strains varied from 129 to 143 bp and 241 to 243 bp, respectively. The sequence of ITS1 was more variable than that of ITS2, while the 5.8S sequences were identical. A phylogenetic tree of the ITS region sequences indicated that the selected strains were classified into three clusters. The reciprocal homologies of the ITS region sequences ranged from 99 to 100%. The strains were also analyzed by random amplification of polymorphic DNA (RAPD) with 20 arbitrary primers. Twelve primers efficiently amplified the genomic DNA. The number of amplified bands varied depending on the primers used or the strains tested. The average number of polymorphic bands observed per primer was 4.5. The size of polymorphic fragments was obtained in the range of 0.2 to 2.3 kb. These results indicate that the RAPD technique is well suited for detecting the genetic diversity in the S. commune strains tested.

  20. A simple model linking galaxy and dark matter evolution

    Energy Technology Data Exchange (ETDEWEB)

    Birrer, Simon; Lilly, Simon; Amara, Adam; Paranjape, Aseem; Refregier, Alexandre, E-mail: simon.birrer@phys.ethz.ch, E-mail: simon.lilly@phys.ethz.ch [Institute for Astronomy, Department of Physics, ETH Zurich, Wolfgang-Pauli-Strasse 27, 8093 Zurich (Switzerland)

    2014-09-20

    We construct a simple phenomenological model for the evolving galaxy population by incorporating predefined baryonic prescriptions into a dark matter hierarchical merger tree. The model is based on the simple gas-regulator model introduced by Lilly et al., coupled with the empirical quenching rules of Peng et al. The simplest model already does quite well in reproducing, without re-adjusting the input parameters, many observables, including the main sequence sSFR-mass relation, the faint end slope of the galaxy mass function, and the shape of the star forming and passive mass functions. Similar to observations and/or the recent phenomenological model of Behroozi et al., which was based on epoch-dependent abundance-matching, our model also qualitatively reproduces the evolution of the main sequence sSFR(z) and SFRD(z) star formation rate density relations, the M{sub s} – M{sub h} stellar-to-halo mass relation, and the SFR – M{sub h} relation. Quantitatively the evolution of sSFR(z) and SFRD(z) is not steep enough, the M{sub s} – M{sub h} relation is not quite peaked enough, and, surprisingly, the ratio of quenched to star forming galaxies around M* is not quite high enough. We show that these deficiencies can simultaneously be solved by ad hoc allowing galaxies to re-ingest some of the gas previously expelled in winds, provided that this is done in a mass-dependent and epoch-dependent way. These allow the model galaxies to reduce an inherent tendency to saturate their star formation efficiency, which emphasizes how efficient galaxies around M* are in converting baryons into stars and highlights the fact that quenching occurs at the point when galaxies are rapidly approaching the maximum possible efficiency of converting baryons into stars.

  1. A six-month double-blind, placebo-controlled, randomized clinical trial of duloxetine for the treatment of fibromyalgia

    Directory of Open Access Journals (Sweden)

    Amy S Chappell

    2008-12-01

    Full Text Available Amy S Chappell1, Laurence A Bradley2, Curtis Wiltse1, Michael J Detke1,3,4, Deborah N D’Souza1, Michael Spaeth51Lilly Research Laboratories, Indianapolis, IN, USA; 2University of Alabama at Birmingham, Birmingham, Alabama, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Harvard Medical School, Boston, MA, USA; 5Practice for Internal Medicine/Rheumatology, Graefelfing, GermanyObjective: Assess the efficacy of duloxetine 60/120 mg (N = 162 once daily compared with placebo (N = 168 in the treatment of patients with fibromyalgia, during six months of treatment.Methods: This was a phase-III, randomized, double-blind, placebo-controlled, parallel-group study assessing the efficacy and safety of duloxetine.Results: There were no significant differences between treatment groups on the co-primary efficacy outcome measures, change in the Brief Pain Inventory (BPI average pain severity from baseline to endpoint (P = 0.053 and the Patient’s Global Impressions of Improvement (PGI-I at endpoint (P = 0.073. Duloxetine-treated patients improved significantly more than placebo-treated patients on the Fibromyalgia Impact Questionnaire pain score, BPI least pain score and average interference score, Clinical Global Impressions of Severity scale, area under the curve of pain relief, Multidimensional Fatigue Inventory mental fatigue dimension, Beck Depression Inventory-II total score, and 36-item Short Form Health Survey mental component summary and mental health score. Nausea was the most common treatment-emergent adverse event in the duloxetine group. Overall discontinuation rates were similar between groups.Conclusions: Although duloxetine 60/120 mg/day failed to demonstrate significant improvement over placebo on the co-primary outcome measures, in this supportive study, duloxetine demonstrated significant improvement compared with placebo on numerous secondary measures.Keywords: fibromyalgia, duloxetine, placebo, double-blind, trial

  2. FIRST LEGO League Kickoff

    Science.gov (United States)

    2007-01-01

    Randall Hicks (right), Jacobs Technology's Education Services manager at NASA John C. Stennis Space Center, answers questions about the playing field for FIRST (For Inspiration and Recognition of Science and Technology) LEGO League's 2007 Challenge, `Power Puzzle.' More than 140 teachers, mentors, parents and students from 15 schools attended the Sept. 15 FLL season kickoff at StenniSphere, the visitor center at SSC. The teams from southern and central Mississippi and Mobile, Ala., who came to SSC heard rules for and asked questions about `Power Puzzle,' and saw robot demonstrations by Gulfport and Picayune high schools' past FIRST Robotics competitions. Using LEGO Mindstorms NXT kits, FLL teams of children ages 9-14 will spend the next three months building and programming robots to perform 'Power Puzzle's' challenge tasks, then pit them in competitions. They also will submit a research project about how energy choices impact the environment and the economy. The season will culminate at the Mississippi Championship Tournament on Dec. 8 at the Mississippi Gulf Coast Community College. FLL, considered the `little league' of the FIRST Robotics Competition, partners FIRST and the LEGO Group. Competitions aim to inspire and celebrate science and technology using real-world context and hands-on experimentation. NASA recognizes FIRST activities as an excellent hands-on method to increase student knowledge of science, engineering, technology and mathematics. Schools represented in this year's kickoff were: Madison Avenue Upper Elementary, the Mississippi Band of Choctaw Indians' Conehatta Elementary, Hattiesburg's Lillie Burney Elementary, Pearl Upper Elementary, Long Beach Middle, Oktibehha Elementary, d'Iberville Middle, Saucier's West Wortham Middle, Picayune's Nicholson Elementary and Roseland Park Baptist Church Academy, Bay St. Louis' St. Stanislaus College and Mobile's Davidson High, as well as two home-school groups from the Jackson area.

  3. Approval summary: pemetrexed maintenance therapy of advanced/metastatic nonsquamous, non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta® Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B(12), and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression-free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash.

  4. Seasonal affective disorder and non-seasonal affective disorders: results from the NESDA study.

    Science.gov (United States)

    Winthorst, Wim H; Roest, Annelieke M; Bos, Elisabeth H; Meesters, Ybe; Penninx, Brenda W J H; Nolen, Willem A; de Jonge, Peter

    2017-07-01

    Seasonal affective disorder (SAD) is considered to be a subtype of depression. To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs). Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire. Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD. SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months. Y.M. has received research funding and served as a consultant for Royal Philips Electronics NV and The Litebook Company Ltd. W.A.N. has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline and Wyeth; has received honoraria/speaker's fees from Astra Zeneca, Pfizer, Servier and Wyeth; and has served in advisory boards for Astra Zeneca, Pfizer and Servier. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

  5. Theory of the nematic quantum critical point in a nodal superconductor

    Science.gov (United States)

    Kim, Eun-Ah

    2008-03-01

    In the last several years, experimental evidence has accumulated in a variety of highly correlated electronic systems of new quantum phases which (for purely electronic reasons) spontaneously break the rotational (point group) symmetry of the underlying crystal. Such electron ``nematic'' phases have been seen in quantum Hall systems[1], in the metamagnetic metal Sr3Ru2O7[2], and more recently in magnetic neutron scattering studies of the high temperature superconductor, YBCO[3]. In the case of a high Tc superconductor, the quantum dynamics of nematic order parameter naturally couples strongly to quasiparticle (qp) excitations. In this talk, I will discuss our recent results on the effects of the coupling between quantum critical nematic fluctuations and the nodal qp's of a d-wave superconductor in the vicinity of a putative quantum critical point inside the superconducting phase. We solve a model system with N flavors of quasiparticles in the large N limit[4]. To leading order in 1/N, quantum fluctuations enhance the dispersion anisotropy of the nodal excitations, and cause strong scattering which critically broadens the quasiparticle peaks in the spectral function, except in the vicinity of ``the tips of the banana,'' where the qp's remain sharp. We will discuss the possible implications of our results to ARPES and STM experiments. [1] M.P. Lilly, K.B. Cooper, J.P. Eisenstein, L.N. Pfeiffer, and K.W. West, PRL 83, 824 (1999). [2] R. A. Borzi and S. A. Grigera and J. Farrell and R. S. Perry and S. J. S. Lister and S. L. Lee and D. A. Tennant and Y. Maeno and A. P. Mackenzie, Science 315, 214 (2007). [3] V. Hinkov, D. Haug, B. Fauqu'e, P. Bourges, Y. Sidis, A. Ivanov, C. Bernhard, C. T. Lin, B. Keimer, unpublished. [4] E.-A. Kim, M. Lawler, P. Oreto, E. Fradkin, S. Kivelson, cond-mat/0705.4099.

  6. Cost minimization analysis of different growth hormone pen devices based on time-and-motion simulations

    Directory of Open Access Journals (Sweden)

    Kim Jaewhan

    2010-04-01

    Full Text Available Abstract Background Numerous pen devices are available to administer recombinant Human Growth Hormone (rhGH, and both patients and health plans have varying issues to consider when selecting a particular product and device for daily use. Therefore, the present study utilized multi-dimensional product analysis to assess potential time involvement, required weekly administration steps, and utilization costs relative to daily rhGH administration. Methods Study objectives were to conduct 1 Time-and-Motion (TM simulations in a randomized block design that allowed time and steps comparisons related to rhGH preparation, administration and storage, and 2 a Cost Minimization Analysis (CMA relative to opportunity and supply costs. Nurses naïve to rhGH administration and devices were recruited to evaluate four rhGH pen devices (2 in liquid form, 2 requiring reconstitution via TM simulations. Five videotaped and timed trials for each product were evaluated based on: 1 Learning (initial use instructions, 2 Preparation (arrange device for use, 3 Administration (actual simulation manikin injection, and 4 Storage (maintain product viability between doses, in addition to assessment of steps required for weekly use. The CMA applied micro-costing techniques related to opportunity costs for caregivers (categorized as wages, non-drug medical supplies, and drug product costs. Results Norditropin® NordiFlex and Norditropin® NordiPen (NNF and NNP, Novo Nordisk, Inc., Bagsværd, Denmark took less weekly Total Time (p ® Pen (GTP, Pfizer, Inc, New York, New York or HumatroPen® (HTP, Eli Lilly and Company, Indianapolis, Indiana. Time savings were directly related to differences in new package Preparation times (NNF (1.35 minutes, NNP (2.48 minutes GTP (4.11 minutes, HTP (8.64 minutes, p Conclusions Time-and-motion simulation data used to support a micro-cost analysis demonstrated that the pen device with the greater time demand has highest net costs.

  7. SU-E-J-134: Optimizing Technical Parameters for Using Atlas Based Automatic Segmentation for Evaluation of Contour Accuracy Experience with Cardiac Structures From NRG Oncology/RTOG 0617

    Energy Technology Data Exchange (ETDEWEB)

    Yu, J; Gong, Y; Bar-Ad, V; Giaddui, T; Galvin, J; Xiao, Y [Thomas Jefferson University, Philadelphia, PA (United States); Hu, C [NRG oncology, Philadelphia, PA (United States); Gore, E; Wheatley, M [Medical College of Wisconsin, Milwaukee, WI (United States); Witt, J; Robinson, C; Bradley, J [Washington University in St. Louis School of Medicine, St. Louis, MO (United States); Kong, F [Georgia Regents University, Augusta, GA (Georgia)

    2015-06-15

    Purpose: Accurate contour delineation is crucial for radiotherapy. Atlas based automatic segmentation tools can be used to increase the efficiency of contour accuracy evaluation. This study aims to optimize technical parameters utilized in the tool by exploring the impact of library size and atlas number on the accuracy of cardiac contour evaluation. Methods: Patient CT DICOMs from RTOG 0617 were used for this study. Five experienced physicians delineated the cardiac structures including pericardium, atria and ventricles following an atlas guideline. The consistency of cardiac structured delineation using the atlas guideline was verified by a study with four observers and seventeen patients. The CT and cardiac structure DICOM files were then used for the ABAS technique.To study the impact of library size (LS) and atlas number (AN) on automatic contour accuracy, automatic contours were generated with varied technique parameters for five randomly selected patients. Three LS (20, 60, and 100) were studied using commercially available software. The AN was four, recommended by the manufacturer. Using the manual contour as the gold standard, Dice Similarity Coefficient (DSC) was calculated between the manual and automatic contours. Five-patient averaged DSCs were calculated for comparison for each cardiac structure.In order to study the impact of AN, the LS was set 100, and AN was tested from one to five. The five-patient averaged DSCs were also calculated for each cardiac structure. Results: DSC values are highest when LS is 100 and AN is four. The DSC is 0.90±0.02 for pericardium, 0.75±0.06 for atria, and 0.86±0.02 for ventricles. Conclusion: By comparing DSC values, the combination AN=4 and LS=100 gives the best performance. This project was supported by NCI grants U24CA12014, U24CA180803, U10CA180868, U10CA180822, PA CURE grant and Bristol-Myers Squibb and Eli Lilly.

  8. Reconnaissance studies of potential petroleum source rocks in the Middle Jurassic Tuxedni Group near Red Glacier, eastern slope of Iliamna Volcano

    Science.gov (United States)

    Stanley, Richard G.; Herriott, Trystan M.; LePain, David L.; Helmold, Kenneth P.; Peterson, C. Shaun

    2013-01-01

    Previous geological and organic geochemical studies have concluded that organic-rich marine shale in the Middle Jurassic Tuxedni Group is the principal source rock of oil and associated gas in Cook Inlet (Magoon and Anders, 1992; Magoon, 1994; Lillis and Stanley, 2011; LePain and others, 2012; LePain and others, submitted). During May 2009 helicopter-assisted field studies, 19 samples of dark-colored, fine-grained rocks were collected from exposures of the Red Glacier Formation of the Tuxedni Group near Red Glacier, about 70 km west of Ninilchik on the eastern flank of Iliamna Volcano (figs. 1 and 3). The rock samples were submitted to a commercial laboratory for analysis by Rock-Eval pyrolysis and to the U.S. Geological Survey organic geochemical laboratory in Denver, Colorado, for analysis of vitrinite reflectance. The results show that values of vitrinite reflectance (percent Ro) in our samples average about 2 percent, much higher than the oil window range of 0.6–1.3 percent (Johnsson and others, 1993). The high vitrinite reflectance values indicate that the rock samples experienced significant heating and furthermore suggest that these rocks may have generated oil and gas in the past but no longer have any hydrocarbon source potential. The high thermal maturity of the rock samples may have resulted from (1) the thermaleffects of igneous activity (including intrusion by igneous rocks), (2) deep burial beneath Jurassic, Cretaceous, and Tertiary strata that were subsequently removed by uplift and erosion, or (3) the combined effects of igneous activity and burial.

  9. SEXUAL DIMORPHISM IN VOLUME OF INSULAR CORTEX IN NORMAL AND NEURODEGENERATIVE HUMAN BRAINS : A STEREOLOGIC AND MACROSCOPIC STUDY

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    H. Haghir

    2005-09-01

    Full Text Available Lillie is known about the sexual differences in volume of human insular cortex in normal subjects and those suffering from ncurodcgcncrativc diseases. The objective of this study is 10 investigate the sex difference in volume of the left insular cortex in normal right-handed subjects versus subjects suffering from Alzheimer and Parkinson diseases. This study was performed on 72 normal human brains (38 males. 34 females. II brains suffered from Alzheimer (4 males. 7 females, and 13 brains suffered from Parkinson (9 males, 4 females. The right hemispheres were used for neuropathologic studies. The volumes of the len insular cortex in the male and female normal subjects were 6.65 :.:: 1.55 em: and 5.X3 ,t: 1.12 em'. respectively (P = 0.0 I. The volumes of the left insular cortex in the male and female subjects suffering from Alzheimer were 5.6X :i.: !.49 ern' and 4.49 :i: (l.X6 em'. respectively (P = 0.2 I. The volumes of the left insular cortex in the male and female subjects suffering from Parkinson were 5.99 ± 1.05 em' und 5.37 ::: 0.51 em'. respectively (P =:= O. I8. The present study shows a significant larger left insular cortex volume in normal right-handed males than in females. No significant sexual difference in volume of the left insular cortex in subjects suffering from Alzheimer and Parkinson diseases W,IS observed. Disappearance of the normal sexual dimorphism in the volume of the insular cortex may be due to a more severe degeneration of this conical area in males during thc ncurodcgcncrativc disorders.

  10. pH measurement and a rational and practical pH control strategy for high throughput cell culture system.

    Science.gov (United States)

    Zhou, Haiying; Purdie, Jennifer; Wang, Tongtong; Ouyang, Anli

    2010-01-01

    The number of therapeutic proteins produced by cell culture in the pharmaceutical industry continues to increase. During the early stages of manufacturing process development, hundreds of clones and various cell culture conditions are evaluated to develop a robust process to identify and select cell lines with high productivity. It is highly desirable to establish a high throughput system to accelerate process development and reduce cost. Multiwell plates and shake flasks are widely used in the industry as the scale down model for large-scale bioreactors. However, one of the limitations of these two systems is the inability to measure and control pH in a high throughput manner. As pH is an important process parameter for cell culture, this could limit the applications of these scale down model vessels. An economical, rapid, and robust pH measurement method was developed at Eli Lilly and Company by employing SNARF-4F 5-(-and 6)-carboxylic acid. The method demonstrated the ability to measure the pH values of cell culture samples in a high throughput manner. Based upon the chemical equilibrium of CO(2), HCO(3)(-), and the buffer system, i.e., HEPES, we established a mathematical model to regulate pH in multiwell plates and shake flasks. The model calculates the required %CO(2) from the incubator and the amount of sodium bicarbonate to be added to adjust pH to a preset value. The model was validated by experimental data, and pH was accurately regulated by this method. The feasibility of studying the pH effect on cell culture in 96-well plates and shake flasks was also demonstrated in this study. This work shed light on mini-bioreactor scale down model construction and paved the way for cell culture process development to improve productivity or product quality using high throughput systems.

  11. Efficacy of tibolone and raloxifene for the maintenance of skeletal muscle strength, bone mineral density, balance, body composition, cognitive function, mood/depression, anxiety and quality of life/well-being in late postmenopausal women ≥ 70 years: Study design of a randomized, double-blind, double-dummy, placebo-controlled, single-center trial

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    Grobbee Diederick E

    2008-06-01

    Full Text Available Abstract Background Postmenopausal women are prone to develop functional disabilities as a result of reduction in muscle strength and muscle mass caused by diminished levels of female sex hormones. While hormone replacement therapy may counteract these changes, conventional hormone replacement therapy is associated with potential harmful effects, such as an increased risk of breast cancer, and its prescription is not recommended. For this reason newer alternative drugs, such as tibolone, a synthetic steroid with estrogenic, progestogenic and androgenic activity, and raloxifene, a selective estrogen receptor modulator, may be more appropriate. This trial investigates the effect of tibolone and raloxifene on muscle strength. Methods We recruited 318 elderly women in our single-center randomized, double-blind, double-dummy, placebo-controlled trial. Participants were randomized to tibolone 1.25 mg (Org OD 14, Organon NV, the Netherlands plus placebo, raloxifene 60 mg (Evista®, Eli Lilly, United States plus placebo or two placebo tablets daily for 24 months. The primary aim is to determine if there is a difference between tibolone and placebo or if there is a difference between raloxifene and placebo. Primary endpoints are muscle strength and bone mineral density. The secondary endpoints are postural balance, body composition, cognitive function, anxiety, mood and quality of life. The secondary aim is to determine if there is a difference between tibolone and raloxifene. The measure of effect is the change from the baseline visit to the visits after 3 months, 6 months, 12 months, and 24 months. A follow-up measurement is planned at 30 months to determine whether any effects are sustained after cessation of the study. By December 2007 the blind will be broken and the data analyzed. Trial registration number NTR: 1232

  12. Antipsychotic adherence, switching, and health care service utilization among Medicaid recipients with schizophrenia

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    Douglas L Noordsy

    2010-07-01

    Full Text Available Douglas L Noordsy1, Glenn A Phillips2, Daniel E Ball2, Walter T Linde-Zwirble31Department of Psychiatry, Dartmouth Medical School, Lebanon, NH, USA; 2Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 3ZD Associates, Perkasie, PA, USAObjective: To evaluate health care resource utilization in patients with schizophrenia who continued newly prescribed antipsychotic medications, compared with those switching to ­different treatments.Methods: Adults with schizophrenia in the California Medicaid (MediCal database who ­initiated treatment with index medications in 1998–2001, were classified as having: 1 ­abandoned antipsychotic medications; 2 switched to another medication; or 3 continued with the index antipsychotic, for up to 6 months after the index date.Results: Of 2300 patients meeting eligibility criteria, 1382 (60.1% continued index medications, 480 (20.9% switched, and 438 (19.0% abandoned antipsychotic treatment. Utilization in several resource categories occurred significantly more frequently among patients whose regimens were switched (vs those continuing index medications. These included using psychiatric (24.2% vs 14.5%; P < 0.001 or nonpsychiatric (31.5% vs 24.3%; P < 0.05 emergency services; being admitted to a hospital (10.6% vs 7.4%; P < 0.05; making nonpsychiatric outpatient hospital visits (43.3% vs 36.4%; P < 0.05 or nonpsychiatric physician visits (62.7% vs 56.4%; P < 0.05; and using other outpatient psychiatric (53.3% vs 40.7%; P < 0.001 or nonpsychiatric (82.7% vs 74.6%; P < 0.001 services.Conclusions: Switching antipsychotic medications is associated with significantly increased health care resource utilization (vs continuing treatment.Keywords: antipsychotics, drug therapy, resource use, treatment adherence

  13. Diagnosis and Treatment of Osteoporosis Before and After Fracture: A Side-by-Side Analysis of Commercially Insured and Medicare Advantage Osteoporosis Patients.

    Science.gov (United States)

    Weaver, Jessica; Sajjan, Shiva; Lewiecki, E Michael; Harris, Steven T

    2017-07-01

    ) to 16.6% (vertebral) among Medicare patients, and 7.5% (NHNV) to 14.4% (vertebral) in Commercial patients. Osteoporosis treatment rates improved significantly in the postfracture year, ranging from 12.5% (NHNV) to 26.5% (vertebral) among Medicare patients, and 8.3% (NHNV) to 21.4% (vertebral) in Commercial patients. Larger increases in diagnosis rates and smaller increases in treatment rates were observed in stratified analyses of men and women and of different age groups, with women and older patients having higher overall rates of diagnosis and treatment before and after fracture. In men and women, osteoporosis diagnosis rates were low before the index fracture and improved substantially after the fracture, yet still remained low overall (under 50%). Osteoporosis treatment rates among patients experiencing a fracture were low before the index fracture and improved only minimally afterwards. This study was funded by Merck & Co. Other than through the employer relationship disclosed here, Merck & Co. did not have a role in the study design, data collection, interpretation of the data, in writing of the manuscript, or in the decision to submit the manuscript for publication. Weaver is an employee of Merck & Co. Sajjan was an employee of Merck & Co. and owned stock in the company at the time of the study. Lewiecki has received consulting and/or speaker honoraria from Merck & Co., AbbVie, AgNovos Healthcare, Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Radius Health, Shire, and TheraNova, along with research grant support from Merck & Co., Amgen, and Eli Lilly and Company, and serves as a board member for the National Osteoporosis Foundation, the International Society for Clinical Densitometry, and the Osteoporosis Foundation of New Mexico. Harris has received consulting honoraria from Merck & Co., Alexion Pharmaceuticals, Amgen, Eli Lilly and Company, Gilead Sciences, Primus Pharmaceuticals, and Radius Health. Study concept and design were contributed by

  14. Eesti autobiograafilise kirjutuse kujunemisest 18. sajandist Teise maailmasõjani. The Development of Estonian Autobiographical Writing from the 18th Century to the Second World War

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    Rutt Hinrikus

    2012-04-01

    Full Text Available In this article I examine the development of Estonian autobiographical writing from its first manifestations to published memoirs, and the development of life writing and its diversification. The beginnings of life writing can be traced back to Estonian folk song and Estonian incidental poetry. The Moravian Brethren movement in Estonia in the 18th century promoted the spread of canonical autobiography. The Moravian Brethren offered alternative opportunities for self-realisation for Estonians who were serfs, and were therefore popular with the people. The practice of the Moravian Brethren made use of retelling and writing about the life of the congregation members, which sometimes became suitable biographies in print, especially stories of awakening. Several manuscript biographies have survived from the Brethren times, such as the biographies of Mäletu Jaan and Mihkel Sarapuu. In addition to the history of the Moravian Brethren movement, these biographies give information about the educational situation and living conditions of the people of the time. The Estonian life writing tradition emerged within the reigning Baltic German cultural space thanks to the Estophiles among the Baltic Germans (J. H. Rosenplänter and the first Estonian men of letters; from the early 19th century we have the diary by Rosenplänter, an estophile pastor from Pärnu, and the diary by the Estonian poet, the then-student Kristjan Jaak Peterson, both in the Estonian language. Johann Voldemar Jannsen, the founder of Estonian-language journalism, kept a diary in the German language for a longer period of time; it was usual that the first Estonian intellectuals (Lilli Suburg, and others in the late 19th century wrote in German. Admittedly, the first Estonian-language life history was written by a forward-looking 19th century peasant named Märt Mitt (1833-1912, who was conscious of himself as a historical subject and gave his memoirs, begun in the 1880s, a memorable title

  15. Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK

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    Gelhorn HL

    2015-11-01

    Full Text Available Heather L Gelhorn,1 Jiat-Ling Poon,1 Evan W Davies,2 Rosirene Paczkowski,3 Sarah E Curtis,3 Kristina S Boye3 1Outcomes Research, Evidera, Bethesda, MD, USA; 2Outcomes Research, Evidera, London, UK; 3Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA Objective: To use a discrete choice experiment (DCE to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide among patients with type 2 diabetes mellitus (T2DM in the UK.Methods: In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: “dosing frequency,” “hemoglobin A1c change,” “weight change,” “type of delivery system,” “frequency of nausea,” and “frequency of hypoglycemia.” Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles.Results: A total of 243 participants [mean age: 60.5 (standard deviation 10.9 years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4 kg/m2] completed the study. RI values for the attributes in rank order were: “dosing frequency” (41.6%, “type of delivery system” (35.5%, “frequency of nausea” (10.4%, “weight change” (5.9%, “hemoglobin A1c change” (3.6%, and “frequency of hypoglycemia” (3.0%. Significantly more participants preferred the dulaglutide profile (83.1% compared with the liraglutide profile (16.9%; P<0.0001.Conclusion: This study elicited patients’ preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications

  16. Spatial distribution and viability of Alexandrium tamarense resting cysts in surface sediments from the St. Lawrence Estuary, Eastern Canada

    Science.gov (United States)

    Gracia, Stéphanie; Roy, Suzanne; Starr, Michel

    2013-04-01

    The dinoflagellate Alexandrium tamarense Group 1 (as defined by Lilly et al., 2007) is responsible for recurrent outbreaks of paralytic shellfish poisoning (PSP) in the St. Lawrence Estuary (SLE), Eastern Canada. In August 2008, a major bloom of A. tamarense developed in the SLE and caused major mortality of fish, seabirds and marine mammals notably in the vicinity of a marine park. Eleven months later, surface (0-5 cm) and deeper (5-10 cm) sediments were sampled to determine resting cysts concentrations, locate prospective cyst seedbeds and examine if these had changed following this major bloom. This information is thought to be important to understand inter-annual patterns in algal toxicity, cyst abundance being a good predictor of subsequent bloom magnitude in some regions. Surface cyst distribution was heterogeneous and it confirmed the location of the cyst seedbed previously reported on the north shore near the Manicouagan/aux-Outardes Rivers (>500 cysts cm-3). A zone of cyst accumulation was also observed on the south shore of the SLE (maximum of 1200 cysts cm-3), with higher concentrations relative to previous cyst mapping in the 1980s. A mismatch was observed between the zones with high surface cyst concentrations and those where the highest PSP toxins were detected (used as a proxy for vegetative cells in the water column). Cyst concentrations were negatively correlated with PSP levels from the same sites, suggesting that cysts were formed and deposited away from the major sites of toxicity. Deposition likely took place near the end of the bloom, once it had reached the eastern boundary of the SLE. PSP toxicity was worse near the peak of the bloom, which occurred westward of this region. This highlights the dynamic behaviour of local blooms, influenced by the estuarine and mesoscale circulation. Interestingly, the major bloom of August 2008 was not followed by particularly large cyst deposition or by any major bloom in 2009 in this region. Cyst viability

  17. A novel derivative of doxorubicin, AD198, inhibits canine transitional cell carcinoma and osteosarcoma cells in vitro

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    Rathore K

    2015-09-01

    Full Text Available Kusum Rathore, Maria Cekanova Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Doxorubicin (DOX is one of the most commonly used chemotherapeutic treatments for a wide range of cancers. N-benzyladriamycin-14-valerate (AD198 is a lipophilic anthracycline that has been shown to target conventional and novel isoforms of protein kinase C (PKC in cytoplasm of cells. Because of the adverse effects of DOX, including hair loss, nausea, vomiting, liver dysfunction, and cardiotoxicity, novel derivatives of DOX have been synthesized and validated. In this study, we evaluated the effects of DOX and its derivative, AD198, on cell viability of three canine transitional cell carcinoma (K9TCC (K9TCC#1-Lillie, K9TCC#2-Dakota, K9TCC#4-Molly and three canine osteosarcoma (K9OSA (K9OSA#1-Zoe, K9OSA#2-Nashville, K9OSA#3-JJ primary cancer cell lines. DOX and AD198 significantly inhibited cell proliferation in all tested K9TCC and K9OSA cell lines in a dose-dependent manner. AD198 inhibited cell viability of tested K9TCC and K9OSA cell lines more efficiently as compared to DOX at the same concentration using MTS (3-(4,5-dimethyl-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2h-tetrazolium assay. AD198 had lower IC50 values as compared to DOX for all tested K9TCC and K9OSA cell lines. In addition, AD198 increased apoptosis in all tested K9TCC and K9OSA cell lines. AD198 increased the caspase activity in tested K9TCC and K9OSA cell lines, which was confirmed by caspase-3/7 assay, and cleavage of poly (ADP-ribose polymerase (PARP was confirmed by Western blotting analysis. In addition, AD198 cleaved PKC-δ, which subsequently activated the p38 signaling pathway, resulting in the apoptosis of tested K9TCC and K9OSA cell lines. Inhibition of the p38 signaling pathway by SB203580 rescued DOX- and AD198-induced apoptosis in tested K9TCC and K9OSA cell lines. Our in vitro results suggest

  18. Environmental concentrations of the selective serotonin reuptake inhibitor fluoxetine impact specific behaviors involved in reproduction, feeding and predator avoidance in the fish Pimephales promelas (fathead minnow).

    Science.gov (United States)

    Weinberger, Joel; Klaper, Rebecca

    2014-06-01

    Pharmaceuticals and personal care products (PPCPs) have been found in surface waters worldwide, but little is understood of their effects on the wildlife that inhabit these waters. Fluoxetine (Prozac; Eli Lilly), a highly prescribed selective serotonin reuptake inhibitor (SSRI), is a commonly found PPCP in surface water. The purpose of this project was to determine if environmentally relevant concentrations of fluoxetine impact behavior that is important for population survival in native fish species, including reproduction, feeding and predator avoidance. Chronic 4-week exposures were conducted with doses ranging from 100 ng/L to 100 μg/L to cover a range of environmentally relevant concentrations up to higher concentrations comparable to other published studies with the same drug that have documented various physiological impacts. Pimephales promelas (fathead minnow), a species native to North America, was used as it conducts a range of specific mating behaviors and therefore serves as an excellent model of specific impacts on brain function. Fluoxetine concentrations as low as 1 μg/L, a concentration that has been found in many freshwater environments, were found to significantly impact mating behavior, specifically nest building and defending in male fish. Males were also found to display aggression, isolation, and repetitive behaviors at higher concentrations. Female mating behavior was largely unaffected. In addition, predator avoidance behaviors in males and females were also impacted at 1 μg/L. Feeding was impacted at 10 μg/L and in the highest exposure (100 μg/L), egg production was limited by deaths of females due to significant male aggressive behaviors in the first two weeks of exposure. Specific behavioral changes occurred at each concentration (most noticeably 1 μg/L and 100 μg/L) indicating a dose dependent effect that triggered different responses at lower exposures versus higher exposures or differential impacts of dose depending on brain

  19. Produção de flores cortadas no estado de Minas Gerais Production of cut flowers in the state o Minas Gerais

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    Paulo Roberto Correa Landgraf

    2009-02-01

    Full Text Available As flores de corte são importantes produtos da floricultura brasileira, as características da produção mineira são, no entanto, desconhecidas. Objetivou-se realizar um estudo da produção de flores de corte no estado de Minas Gerais, aplicou-se um questionário aos produtores do Estado , no período de 2003 a 2005. As visitas foram feitas in loco e os produtores foram identificados por meio de visitas nas áreas produtivas e os questionários foram respondidos por eles próprios. Analisando-se as respostas contidas nos questionários, identificou-se que a produção de flores de corte no estado de Minas Gerais é uma atividade realizada por 188 produtores, numa área plantada de aproximadamente 290,6836 ha As principais espécies cultivadas no Estado são: rosa (151,5710, sempre-vivas (57,26 ha, copo-de-leite (16,0255 ha, cravo (12,6290 ha e helicônia (11,7600 ha. A produção é vendida para o todo o Brasil e também exportada para países da Europa, Ásia e América do Norte. Os principais produtos exportados são: rosas de corte, orquídeas de corte e sempre-vivas.Cut flowers are important products of Brazilian floriculture. The characteristics of Minas Gerais production are, nevertheless, unknown. So, with the purpose of performing a study of the cut flower production in the state of Minas Gerais, a questionnaire was applied to flower growers of Minas Gerais state, in the period of 2003 to 2005. The visits were paid in loco and the growers were identified by means of visits to the flower-growing areas and the questionnaires were answered by them. By analyzing the answers contained in the questionnaires, it was identified that the cut flower production in the state of Minas Gerais is a business accomplished by 188 growers in a planted area of about 290.6836 ha. The main species grown in the state are: rose (151.5710 ha, sempre-vivas (57.26 ha, cala lilly flowers (16.0255 ha, carnation (12.6290 ha and heliconia (11.7600 ha. The

  20. Loss to follow up within an HIV cohort

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    H Wood

    2012-11-01

    Full Text Available BHIVA guidelines recommend that all ARV-naïve and stable on-treatment patients are monitored at least 6 monthly [1]. Studies have shown that loss to follow up (LFU not only worsens outcomes [2] but has increased potential for onward transmission. Case notes of 1275 HIV patients registered under our care up to January 2011 were examined for attendance within the previous 6 months. 788 (61% patients had not been seen within the previous 6 months. Reasons for non attendance were identified. These are outlined below: 76% of the 130 LFU whose demographics were further examined were of Black African ethnicity, 54% female, 51% of single marital status and 48% of patients had been taking ARVs at the time of LFU. Interestingly, 53% of patients were lost to follow up within 1 year of diagnosis. The LFU patients (88 that had a local GP and a registered current address were sent recall letters. A small number of patients reengaged with care as a result of this action, some having not attended for over 5 years. Partner notification led to a number of new diagnoses in these cases. Failure to respond led to subsequent letters inviting them to clinic and finally a letter to their GP informing them of non attendance. In September 2011, a new recall system using Lillie Electronic Patient Records (EPR was introduced to promptly recognise if a patient had not attended for care as planned. Prior to this, recall was a manual process carried out by the Health Advising Team. We conclude that within our cohort we had a particularly mobile group of patients; 455 (36% transferring care to another clinic within the UK, 54 (4% moving out of UK. 76% of the LFU group being of Black African ethnicity highlights the ongoing problem of retention of care in this group. Further exploration is needed to identify additional issues besides housing and immigration that lead to LFU. Furthermore, the disportionate number of patients (53% disengaging with services within 1 year of

  1. Real-world comparison of health care utilization between duloxetine and pregabalin initiators with fibromyalgia

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    Peng X

    2014-01-01

    Full Text Available X Peng,1 P Sun,2 D Novick,1 J Andrews,1 S Sun2 1Eli Lilly and Company, Indianapolis, IN, USA; 2Kailo Research Group, Indianapolis, IN, USA Objectives: To compare health care utilization of duloxetine initiators and pregabalin initiators among fibromyalgia patients in a real-world setting. Methods: A retrospective cohort study was conducted based on a US national commercial health claims database (2006–2009. Fibromyalgia patients who initiated duloxetine or pregabalin in 2008, aged 18–64 years, and who maintained continuous health insurance coverage 1 year before and 1 year after initiation were assigned to duloxetine or pregabalin cohorts on the basis of their initiated agent. Patients who had pill coverage of the agents over the course of 90 days preceding the initiation were excluded. The two comparative cohorts were constructed using propensity score greedy match methods. Descriptive analysis and paired t-test were performed to compare health care utilization rates in the postinitiation year and the changes of these rates from the preinitiation year to the postinitiation year. Results: Both matched cohorts (n=1,265 pairs had a similar mean initiation age (49–50 years, percentage of women (87%–88%, and prevalence of baseline comorbid conditions (neuropathic pain other than diabetic peripheral neuropathic pain, low back pain, cardiovascular disease, hypertension, headache or migraine, and osteoarthritis. In the preinitiation year, both cohorts had similar inpatient, outpatient, and medication utilization rates (inpatient, 15.7%–16.1%; outpatient, 100.0%; medication, 97.9%–98.7%. The utilization rates diverged in the postinitiation year, with the pregabalin cohort using more fibromyalgia-related inpatient care (3.2% versus 2.2%; P<0.05, any inpatient care (19.3% versus 16.8%; P<0.05, and fibromyalgia-related outpatient care (62.1% versus 51.8%; P<0.05. From the preinitiation period to the postinitiation period, the duloxetine cohort

  2. On the role of the stratosphere in the process of overflow of mesoscale mountains

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    K. B. Moiseenko

    2005-12-01

    Full Text Available A 2-D, two- and three-layer stratified airflow over a mountain of arbitrary shape is considered on the assumptions that upstream wind velocity and static stability within each layer are constant (Long's model. The stratosphere is simulated by an infinitely deep upper layer with enhanced static stability.

    The analytical solution for the stream function, as well as first (linear and second order approximations to the wave drag, are obtained in hydrostatic limit N1L/U0→∞, where N1 is the Brunt-Väsälä frequency in the troposphere, L is a characteristic length of the obstacle, and U0 is upstream velocity. The results of numerical computations show the principal role of long waves in the process of interaction between the model layers for a typical mesoscale mountains for which the hydrostatic approximation proves valid in a wide range of flow parameters, in accordance with the earlier conclusions of Klemp and Lilly (1975. Partial reflection of wave energy from the tropopause produces strong influence on the value of wave drag for typical middle and upper tropospheric lapse rates, leading to a quasi-periodic dependance of wave drag on a reduced frequency $k{=}N_1{tilde H}/pi U_0$ (${tilde H}$ is tropopause height in the troposphere. The flow seems to be statically unstable for k≥2 for sufficiently large obstacles (whose height exceeds 1 km. In this case, vast regions of rotor motions and strong turbulence are predicted from model calculations in the middle troposphere and the lower stratosphere. The model calculations also point to a testify

  3. Risk factors associated with metabolic syndrome in type 2 diabetes mellitus patients according to World Health Organization, Third Report National Cholesterol Education Program, and International Diabetes Federation definitions

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    Angel Rodríguez

    2010-12-01

    Full Text Available Angel Rodríguez1, Helena Delgado-Cohen1, Jesús Reviriego1, Manuel Serrano-Ríos21Clinical Research Department, Eli Lilly and Company, Madrid, Spain; 2Department of Internal Medicine II, Hospital Clinico San Carlos, Madrid, SpainBackground: The availability of several definitions of the metabolic syndrome has created potential confusion concerning its prognostic utility. At present, little data exist about the risk factors associated with metabolic syndrome in diabetic patients.Aim: To identify risk factors associated with metabolic syndrome in patients with type 2 diabetes mellitus according to three diagnostic criteria: World Health Organization (WHO, Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults – Adult Treatment Panel III (NCEP-ATP III, and International Diabetes Federation (IDF.Subjects and methods: A logistic regression model was used to identify demographic, clinical, and lifestyle variables related with metabolic syndrome (N = 1259.Results: Hypertension, dyslipidemia, and glycosylated hemoglobin (HbA1c ≥7% were associated with increased risk of WHO-defined metabolic syndrome (odds ratio [OR], 2.33; 95% confidence interval [CI]: 1.60–3.40; OR, 1.79 95% CI: 1.25–2.55; and OR, 1.58; 95% CI: 1.12–2.22, respectively. The risk of presenting metabolic syndrome according to NCEP-ATP III criteria was increased in female patients (OR, 2.02; 95% CI: 1.37–2.97, elevated fasting glucose levels (OR, 5.99; 95% CI: 3.56–10.07, dyslipidemia (OR, 2.28; 95% CI: 1.57–3.32, hypertension (OR, 2.36; 95% CI: 1.59–3.53, and endocrine disorders (OR, 1.64; 95% CI: 1.06–2.57. For the IDF criteria, female patients and patients with left ventricular hypertrophy or insulin treatment were at higher risk of metabolic syndrome (OR, 4.00; 95% CI: 2.35–6.80; OR, 2.72 95% CI: 1.22–6.04; and OR, 1.96 95% CI: 1.24–3.11, respectively.Conclusions: The

  4. The cost-effectiveness of a NSCLC patient assistance program for pemetrexed maintenance therapy in People’s Republic of China

    Science.gov (United States)

    Shi, Qiang; Hu, Shanlian; Furnback, Wesley E; Guzauskas, Gregory F; Shen, Jiejing; Wang, Bruce CM

    2017-01-01

    Background Eli Lilly and the China Primary Health Care Foundation are currently implementing a patient assistance program (PAP) in China, which allows first-line nonsquamous non-small-cell lung cancer (NSCLC) patients who complete four cycles of pemetrexed induction therapy to receive free, continuous pemetrexed maintenance therapy. Objective To estimate the cost-effectiveness of pemetrexed maintenance therapy vs basic standard care (BSC) and the economic impacts of providing a PAP for pemetrexed maintenance therapy to NSCLC patients who have completed pemetrexed induction therapy in a Chinese health care setting. Methods We developed a novel decision-analytic model to evaluate the long-term costs and clinical efficacy of pemetrexed plus BSC vs BSC alone. We utilized a three-state (progression-free survival, progressed disease, and dead) partition survival model for both the clinical and economic aspects of the analysis. Cost and health utility estimates were derived from the literature. We performed a scenario analysis to estimate the real-world impact of introducing the PAP in China by comparing the use of the PAP vs non-PAP. Model uncertainty was evaluated using one-way and multivariate probabilistic sensitivity analysis. Results Compared to BSC, pemetrexed plus BSC resulted in a gain of 0.22 years of life (95% credible range [CR]: 0.04–0.46) and 0.13 quality-adjusted life years (95% CR: 0.04–0.26) per patient, at an increased cost of $28,105 (95% CR: −$22,720 to $48,646) without a PAP and $3,068 (95% CR: −$1,263 to $9,163) with a PAP. The incremental cost-effectiveness ratio for pemetrexed plus BSC vs BSC alone was cost-prohibitive at $222,700 for non-PAP, but cost-effective at $24,319 with a PAP. Conclusion Our study suggests that maintenance pemetrexed therapy following pemetrexed induction for patients with advanced NSCLC is likely to be highly non-cost-effective in the absence of a PAP, but the pending implementation of the PAP promises to make it

  5. Perspectives on future Alzheimer therapies: amyloid-β protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer's disease.

    Science.gov (United States)

    Lannfelt, Lars; Möller, Christer; Basun, Hans; Osswald, Gunilla; Sehlin, Dag; Satlin, Andrew; Logovinsky, Veronika; Gellerfors, Pär

    2014-01-01

    The symptomatic drugs currently on the market for Alzheimer's disease (AD) have no effect on disease progression, and this creates a large unmet medical need. The type of drug that has developed most rapidly in the last decade is immunotherapy: vaccines and, especially, passive vaccination with monoclonal antibodies. Antibodies are attractive drugs as they can be made highly specific for their target and often with few side effects. Data from recent clinical AD trials indicate that a treatment effect by immunotherapy is possible, providing hope for a new generation of drugs. The first anti-amyloid-beta (anti-Aβ) vaccine developed by Elan, AN1792, was halted in phase 2 because of aseptic meningoencephalitis. However, in a follow-up study, patients with antibody response to the vaccine demonstrated reduced cognitive decline, supporting the hypothesis that Aβ immunotherapy may have clinically relevant effects. Bapineuzumab (Elan/Pfizer Inc./Johnson & Johnson), a monoclonal antibody targeting fibrillar Aβ, was stopped because the desired clinical effect was not seen. Solanezumab (Eli Lilly and Company) was developed to target soluble, monomeric Aβ. In two phase 3 studies, Solanezumab did not meet primary endpoints. When data from the two studies were pooled, a positive pattern emerged, revealing a significant slowing of cognitive decline in the subgroup of mild AD. The Arctic mutation has been shown to specifically increase the formation of soluble Aβ protofibrils, an Aβ species shown to be toxic to neurons and likely to be present in all cases of AD. A monoclonal antibody, mAb158, was developed to target Aβ protofibrils with high selectivity. It has at least a 1,000-fold higher selectivity for protofibrils as compared with monomers of Aβ, thus targeting the toxic species of the peptide. A humanized version of mAb158, BAN2401, has now entered a clinical phase 2b trial in a collaboration between BioArctic Neuroscience and Eisai without the safety concerns seen

  6. Do different clinical evidence bases lead to discordant health-technology assessment decisions? An in-depth case series across three jurisdictions

    Directory of Open Access Journals (Sweden)

    Spinner DS

    2013-01-01

    Full Text Available Daryl S Spinner,1 Julie Birt,2 Jeffrey W Walter,1 Lee Bowman,2 Josephine Mauskopf,1 Michael F Drummond,3 Catherine Copley-Merriman11RTI Health Solutions, Research Triangle Park, NC, USA; 2Eli Lilly and Company, Indianapolis, IN, United States; 3University of York, York, UKBackground: Health-technology assessment (HTA plays an important role in informing drug-reimbursement decision-making in many countries. HTA processes for the Pharmaceutical Benefits Advisory Committee (PBAC in Australia, the Common Drug Review (CDR in Canada, and the National Institute for Health and Clinical Excellence (NICE in England and Wales are among the most established in the world. In this study, we performed nine in-depth case studies to assess whether different clinical evidence bases may have influenced listing recommendations made by PBAC, CDR, and NICE.Methods: Nine drugs were selected for which the three agencies had provided listing recommendations for the same indication between 2007 and 2010. We reviewed the evidence considered for each listing recommendation, identified the similarities and differences among the clinical evidence bases considered, and evaluated the extent to which different clinical evidence bases could have contributed to different decisions based on HTA body comments and public assessment of the evidence.Results: HTA agencies reached the same recommendation for reimbursement (recommended for listing for four drugs and different recommendations for five drugs. In all cases, each agency used different evidence bases in their recommendations. The agencies considered overlapping sets of clinical comparators and trials when evaluating the same drug. While PBAC and NICE considered indirect and/or mixed-treatment comparisons, CDR did not. In some cases, CDR and/or NICE excluded trials from review if the drug and/or the comparator were not administered according to the relevant marketing authorization.Conclusions: In the listing recommendations

  7. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

    Directory of Open Access Journals (Sweden)

    Berteau C

    2015-11-01

    Full Text Available Cecile Berteau,1 Orchidée Filipe-Santos,1 Tao Wang,2 Humberto E Rojas,2 Corinne Granger,1 Florence Schwarzenbach1 1Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France; 2Eli Lilly and Company, Indianapolis, IN, USA Aim: The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC injection pain tolerance. Methods: The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8–10, and 15–20 cP combined with two different injection flow rates (0.02 and 0.3 mL/s. All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS (0 mm/no pain, 100 mm/extreme pain. The location and depth of the injected fluid was assessed through 2D ultrasound echography images. Results: Viscosity levels had significant impact on perceived injection pain (P=0.0003. Specifically, less pain was associated with high viscosity (VAS =12.6 mm than medium (VAS =16.6 mm or low (VAS =22.1 mm viscosities, with a significant difference between high and low viscosities (P=0.0002. Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89. Slow (0.02 mL/s or fast (0.30 mL/s injection rates also showed no significant impact on perceived pain during SC injection (P=0.79. In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers. Conclusion: The results of this study suggest that solutions of up to 3 mL and up to 15–20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High

  8. Preference for pharmaceutical formulation and treatment process attributes

    Directory of Open Access Journals (Sweden)

    Stewart KD

    2016-07-01

    Full Text Available Katie D Stewart,1 Joseph A Johnston,2 Louis S Matza,1 Sarah E Curtis,2 Henry A Havel,3 Stephanie A Sweetana,3 Heather L Gelhorn1 1Outcomes Research, Evidera, Bethesda, MD, USA; 2Global Patient Outcomes & Real World Evidence, 3Small Molecule Design and Development, Eli Lilly & Company, Indianapolis, IN, USA Purpose: Pharmaceutical formulation and treatment process attributes, such as dose frequency and route of administration, can have an impact on quality of life, treatment adherence, and disease outcomes. The aim of this literature review was to examine studies on preferences for pharmaceutical treatment process attributes, focusing on research in diabetes, oncology, osteoporosis, and autoimmune disorders.Methods: The literature search focused on identifying studies reporting preferences for attributes of the pharmaceutical treatment process. Studies were required to use formal quantitative preference assessment methods, such as utility valuation, conjoint analysis, or contingent valuation. Searches were conducted using Medline, EMBASE, Cochrane Library, Health Economic Evaluation Database, and National Health Service Economic Evaluation Database (January 1993–October 2013.Results: A total of 42 studies met inclusion criteria: 19 diabetes, nine oncology, five osteoporosis, and nine autoimmune. Across these conditions, treatments associated with shorter treatment duration, less frequent administration, greater flexibility, and less invasive routes of administration were preferred over more burdensome or complex treatments. While efficacy and safety often had greater relative importance than treatment process, treatment process also had a quantifiable impact on preference. In some instances, particularly in diabetes and autoimmune disorders, treatment process attributes had greater relative importance than some or all efficacy and safety attributes. Some studies suggested that relative importance of treatment process depends on disease (eg

  9. Can Chronic Pain Patients Be Adequately Treated Using Generic Pain Medications to the Exclusion of Brand-Name Ones?

    Science.gov (United States)

    Candido, Kenneth D; Chiweshe, Joseph; Anantamongkol, Utchariya; Knezevic, Nebojsa Nick

    2016-01-01

    According to the Food and Drug Administration (FDA) reports, approximately 8 in 10 prescriptions filled in the United States are for generic medications, with an expectation that this number will increase over the next few years. The impetus for this emphasis on generics is the cost disparity between them and brand-name products. The use of FDA-approved generic drugs saved 158 billion dollars in 2010 alone. In the current health care climate, there is continually increasing pressure for prescribers to write for generic alternative medications, occasionally at the expense of best clinical practices. This creates a conflict wherein both physicians and patients may find brand-name medications clinically superior but nevertheless choose generic ones. The issue of generic versus brand medications is a key component of the discussion of health payers, physicians and their patients. This review evaluates some of the important medications in the armamentarium of pain physicians that are frequently used in the management of chronic pain, and that are currently at the forefront of this issue, including Opana (oxymorphone; Endo Pharmaceuticals, Inc., Malvern, PA), Gralise (gabapentin; Depomed, Newark, CA), and Horizant (gabapentin enacarbil; XenoPort, Santa Clara, CA) that are each available in generic forms as well. We also discuss the use of Lyrica (pregabalin; Pfizer, New York, NY), which is currently unavailable as generic medication, and Cymbalta (duloxetine; Eli Lilly, Indianapolis, IN), which has been recently FDA approved to be available in a generic form. It is clear that the use of generic medications results in large financial savings for the cost of prescriptions on a national scale. However, cost-analysis is only part of the equation when treating chronic pain patients and undervalues the relationships of enhanced compliance due to single-daily dosing and stable and reliable pharmacokinetics associated with extended-duration preparations using either retentive

  10. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

  11. The mass-metallicity and fundamental metallicity relations at z > 2 using very large telescope and Subaru near-infrared spectroscopy of zCOSMOS galaxies

    Energy Technology Data Exchange (ETDEWEB)

    Maier, C.; Ziegler, B. L. [Department of Astrophysics, University of Vienna, Türkenschanzstrasse 17, A-1180 Vienna (Austria); Lilly, S. J.; Peng, Y. [Institute of Astronomy, ETH Zurich, Wolfgang-Pauli-Strasse 27, CH-8093 Zurich (Switzerland); Contini, T. [Institut de Recherche en Astrophysique et Planétologie, CNRS, 14 avenue Édouard Belin, F-31400 Toulouse (France); Pérez Montero, E. [Instituto de Astrofísica de Andalucia, CSIC, Apartado de Correos 3004, E-18080 Granada (Spain); Balestra, I., E-mail: christian.maier@univie.ac.at [Max-Planck-Institut für Extraterrestrische Physik, Postfach 1312, Giessenbachstrasse, D-85741 Garching b. München (Germany)

    2014-09-01

    In the local universe, there is good evidence that, at a given stellar mass M, the gas-phase metallicity Z is anti-correlated with the star formation rate (SFR) of the galaxies. It has also been claimed that the resulting Z(M, SFR) relation is invariant with redshift—the so-called 'fundamental metallicity relation' (FMR). Given a number of difficulties in determining metallicities, especially at higher redshifts, the form of the Z(M, SFR) relation and whether it is really independent of redshift is still very controversial. To explore this issue at z > 2, we used VLT-SINFONI and Subaru-MOIRCS near-infrared spectroscopy of 20 zCOSMOS-deep galaxies at 2.1 < z < 2.5 to measure the strengths of up to five emission lines: [O II] λ3727, Hβ, [O III] λ5007, Hα, and [N II] λ6584. This near-infrared spectroscopy enables us to derive O/H metallicities, and also SFRs from extinction corrected Hα measurements. We find that the mass-metallicity relation (MZR) of these star-forming galaxies at z ≈ 2.3 is lower than the local Sloan Digital Sky Survey (SDSS) MZR by a factor of three to five, a larger change than found by Erb et al. using [N II]/Hα-based metallicities from stacked spectra. We discuss how the different selections of the samples and metallicity calibrations used may be responsible for this discrepancy. The galaxies show direct evidence that the SFR is still a second parameter in the MZR at these redshifts. However, determining whether the Z(M, SFR) relation is invariant with epoch depends on the choice of extrapolation used from local samples, because z > 2 galaxies of a given mass have much higher SFRs than the local SDSS galaxies. We find that the zCOSMOS galaxies are consistent with a non-evolving FMR if we use the physically motivated formulation of the Z(M, SFR) relation from Lilly et al., but not if we use the empirical formulation of Mannucci et al.

  12. Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel: a 1-year follow-up from the European MULTIPRAC Registry

    Directory of Open Access Journals (Sweden)

    Goldstein P

    2016-04-01

    Full Text Available Patrick Goldstein,1 Niccolò Grieco,2 Hüseyin Ince,3,4 Nicolas Danchin,5 Yvonne Ramos,6 Jochen Goedicke,7 Peter Clemmensen8,9 On behalf of the MULTIPRAC study investigators 1Emergency Department, Lille Regional University Hospital, Lille, France; 2Department of Cardiology, Hospital Niguarda Cà Granda Milano, Milan, Italy; 3Internal Medicine Centre, Cardiology Department, Rostock University Clinic, Rostock, Germany; 4Department of Cardiology, Vivantes Klinikum im Friedrichshain and Am Urban, Berlin, Germany; 5Department of Cardiology, European Hospital Georges-Pompidou, Paris, France; 6Medical Department, Daiichi Sankyo Europe, Munich, 7Medical Department, Lilly Deutschland GmbH, Bad Homburg, Germany; 8Department of Medicine, Division of Cardiology, Rigshospitalet Copenhagen University Hospital, 9Department of Medicine, Division of Cardiology, Nykoebing F Hospital, Copenhagen, Denmark Aim: MULTIPRAC was designed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention. After a previous report on efficacy and safety outcomes during hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV mortality. Methods and results: MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI from 25 hospitals in nine countries, all of which had an established practice of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2,036 patients followed-up through 1 year, 49 died (2.4%, 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used from prehospital loading dose through hospital discharge. Prasugrel (n=824 was more commonly used than clopidogrel (n=425. The observed 1-year rates for CV death

  13. Comparing common reasons for inpatient and outpatient visits between commercially-insured duloxetine or pregabalin initiators with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2012-10-01

    Full Text Available Yang Zhao,1 Peter Sun,2 Mark Bernauer31Eli Lilly and Company, 2Kailo Research Group, 3OptumInsight, Indianapolis, IN, USABackground: The purpose of this study was to examine the main reasons for inpatient or outpatient visits after initiating duloxetine or pregabalin.Methods: Commercially insured patients with fibromyalgia and aged 18–64 years who initiated duloxetine or pregabalin in 2006 with 12-month continuous enrollment before and after initiation were identified. Duloxetine and pregabalin cohorts with similar demographics, pre-index clinical and economic characteristics, and pre-index treatment patterns were constructed via propensity scoring stratification. Reasons for inpatient admissions, physician office visits, outpatient hospital visits, emergency room visits, and primary or specialty care visits over the 12 months post-index period were examined and compared. Logistic regression was used to assess the contribution of duloxetine versus pregabalin initiation to the most common reasons for visits, controlling for cross-cohort differences.Results: Per the study design, the duloxetine (n = 3711 and pregabalin (n = 4111 cohorts had similar demographics (mean age 51 years, 83% female and health care costs over the 12-month pre-index period. Total health care costs during the 12-month post-index period were significantly lower for duloxetine patients than for pregabalin patients ($19,378 versus $27,045, P < 0.05. Eight of the 10 most common reasons for inpatient admissions and outpatient hospital (physician office, emergency room, primary or specialty care visits were the same for both groups. Controlling for cross-cohort differences, duloxetine patients were less likely to be hospitalized due to an intervertebral disc disorder or major depressive disorder, to have a physician office visit due to nonspecific backache/other back/neck pain (NB/OB/NP disorder, or to go to specialty care due to a soft tissue, NB/OP/NP, or intervertebral disc

  14. "Alguses oli tema üksinda, sest oli küll..." : [luuletused] / Kabir ; tlk. Doris Kareva

    Index Scriptorium Estoniae

    Kabir

    2006-01-01

    Sisu: "Alguses oli tema üksinda, sest oli küll..." ; "Kõik loodud on Kõiksuse poolt..." ; "Otsid Sa mind?..." ; "Kabir oma meele puhtaks..." ; "Pole pühades järvedes midagi muud peale vee..." ; "Otsisin kelme ja kõveraid..." ; "Ütle, vend, mida küll teha..." ; "Mis kurja on teinud su juuksed..." ; "Ära tõuse, et minna õue vaatama lilli..." ; "Sinu sünd inimesena on küps vili..." ; "Öö saatsid sa magades mööda..." ; "Pole ma hindu..." ; "Ma vaatan sind..." ; "Veskikivisid vaadeldes ; "Nähes aednikku lähenemas, õhkasid pungad..." ; "Tasa, tasa tõtta, mu meel..." ; "Ära kurvasta..." ; "Imetlusväärne on teemant..." ; "Kuula, sõber, see keha on Tema lüüra..." ; "Nagu seemnes varjul on õli..." ; "Olgugi ookean leekides..." ; "Tilka, mis lahustub meres..." ; "Jõgi ja lained on üks..." ; "Kes sa oled ja kust oled tulnud?..." ; "Kaovad kuningad, kauneimad kuningannad..." ; "Rohkem kui midagi muud..." ; "Lihalik, surelik tantsib selle ees..." ; "Väike rubiin, mida igaüks ihkab..." ; "Mine heade juurde, kus Armastatugi elab..." ; "Eksitus sulgeb väravad..." ; "Keelilt vallandub helisid..." ; "Kõik algab lahusoleku valust..." ; "Ärka, sõber! Miks ikka veel magad?..." ; "Kuu on mu kehas, kuid ise ma seda ei näe..." ; "Miks oled nii kärsitu, süda?..." ; "Kellele kuulub see flööt..." ; "Kui raske on Külalist kohata!..." ; "Kandetool toodi minule järgi mu isakoju..." ; "Siia ilma sündides nutsid..." ; "Oh mu süda! Ei jõudnud sa tundma õppida..." ; "Õige kulunud on sinu rüü..." ; "Õhkõrn on see õhuke rüü..." ; "Lipp, mida keegi ei näe..." ; "Oh otsija, lihtne liit lähim on südamele..." ; "Õhtu varjud on sügavaks saanud..." ; "Kuis saakski katkeda armastus me kahe vahel..." ; "Luik, tahaksin, et mulle räägiksid kõik oma loo..." ; "Kuhu ihaled küll, minu süda?..." ; "Ei lakka Lõpmatu flöödiheli..." ; "Mida näed, seda pole...". Autori kohta eluloolisi andmeid lk. 11

  15. Predictors of duloxetine adherence and persistence in patients with fibromyalgia

    Directory of Open Access Journals (Sweden)

    Cui Z

    2012-06-01

    Full Text Available Zhanglin Cui, Yang Zhao, Diego Novick, Douglas FariesEli Lilly and Company, Indianapolis, IN, USAObjectives: Adherence to medication for the treatment of fibromyalgia (FM is predictive of lower overall health-care costs, and thus a lower burden on both patients and providers. The objectives of this study were to examine the predictors of adherence to and persistence with duloxetine therapy among commercially insured FM patients, and to identify subgroups of patients with high duloxetine persistence and adherence.Study design: This cross-sectional, retrospective study analyzed medical and pharmacy records over 1 year for patients in the US aged 18–64 years with FM who initiated (no prior 90-day use duloxetine treatment in 2008.Methods: Adherence to duloxetine was measured by medication possession ratio (MPR, with high adherence defined as MPR ≥ 0.8. Persistence was defined as the duration of therapy from the index date to the earliest of: the ending date of the last prescription, the date of the first gap of >15 days between prescriptions, or the end of the study period (12 months. Demographic and clinical predictors of adherence were examined via multiple logistic regression (MLR, and subgroups of duloxetine-persistent and -adherent patients were identified using classification and regression trees (CART.Results: Among 4660 duloxetine patients, 33% achieved high adherence. Factors associated with high adherence from MLR included older age, North Central and Northeast regions, prior venlafaxine, pregabalin, selective serotonin reuptake inhibitor (SSRI, or other antidepressant use, or comorbid dyslipidemia or osteoarthritis (all P < 0.05. CART analysis revealed that patients with prior antidepressant use, aged ≥46, or prior osteoarthritis had higher MPR (all P < 0.05, and patients aged ≥45 with a history of SSRI, venlafaxine, or anticonvulsant use had longer duration of therapy (all P < 0.05.Conclusions: Patients with high adherence to and

  16. Real-world treatment patterns and opioid use in chronic low back pain patients initiating duloxetine versus standard of care

    Directory of Open Access Journals (Sweden)

    Andrews JS

    2013-11-01

    Full Text Available Jeffrey Scott Andrews,1 Ning Wu,2 Shih-Yin Chen,2 Xia Yu,2 Xiaomei Peng,1 Diego Novick1 1Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Evidera, Lexington, MA, USA Abstract: To describe the use of pain medications in patients with chronic low back pain (CLBP after initiating duloxetine or standard of care (SOC [muscle relaxants, gabapentin, pregabalin, venlafaxine, and tricyclic antidepressants] for pain management, pharmacy and medical claims from Surveillance Data, Inc (SDI Health were analyzed. Adult patients with CLBP who initiated duloxetine or SOC between November 2010 and April 2011 were identified. Treatment initiation was defined as no pill coverage for duloxetine or SOC in the previous 90 days. Included patients had no opioid use in the 90 days before initiation. Propensity score matching was used to select patients with similar baseline demographic and clinical characteristics for duloxetine and SOC cohorts. Compliance with index medication was assessed via medication possession ratio (MPR and proportion of days covered (PDC for 6 months after initiation. The proportion of patients receiving opioids and days on opioids after index date were assessed, and regression models were estimated to compare opioid use between cohorts. A total of 766 patients initiated duloxetine and 6,206 patients initiated SOC. After matching, 743 patients were selected for the duloxetine (mean age 57 years; female 74% and SOC (mean age 57 years; female 75% cohorts, respectively. Of the duloxetine cohort, 92% started on or below recommended daily dose (≤60 mg. The duloxetine cohort had significantly higher MPR (0.78 versus [vs] 0.60 and PDC (0.50 vs 0.31, were less likely to use opioids (45% vs 61%, and had fewer days on opioids (median 0 vs 7 days than the SOC cohort (all P < 0.001. After adjusting for demographic and clinical characteristics, the duloxetine cohort initiated opioids later than the SOC cohort (hazard ratio 0.77, 95

  17. The relationship between cholesterol and cognitive function is homocysteine-dependent

    Directory of Open Access Journals (Sweden)

    Cheng YB

    2014-10-01

    Full Text Available Yibin Cheng,1 Yinlong Jin,1 Frederick W Unverzagt,2 Liqin Su,1 Lili Yang,3 Feng Ma,1 Ann M Hake,4,5 Carla Kettler,3 Chen Chen,1 Jingyi Liu,1 Jianchao Bian,6 Ping Li,7 Jill R Murrell,8 Hugh C Hendrie,2,9,10 Sujuan Gao3 1Institute for Environmental Health and Related Product Safety, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Psychiatry, 3Department of Biostatistics, 4Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA; 5Eli Lilly and Company, Indianapolis, Indiana, USA; 6Shandong Institute for Prevention and Treatment of Endemic Disease in China, Jinan, People’s Republic of China; 7Sichuan Provincial Center for Disease Control and Prevention in China, Chengdu, People’s Republic of China; 8Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 9Indiana University Center for Aging Research, 10Regenstrief Institute, Inc., Indianapolis, Indiana, USA Introduction: Previous studies have identified hyperlipidemia as a potential risk factor for dementia and Alzheimer’s disease. However, studies on cholesterol measured in late-life and cognitive function have been inconsistent. Few studies have explored nonlinear relationships or considered interactions with other biomarker measures.Methods: A cross-sectional sample of 1,889 participants from four rural counties in the People’s Republic of China was included in this analysis. Serum total cholesterol, high-density lipoprotein, triglycerides, and homocysteine levels were measured in fasting blood samples. A composite cognitive score was derived based on nine standardized cognitive test scores. Analysis of covariance models were used to investigate the association between biomarker measures and the composite cognitive scores.Results: There was a significant interaction between the homocysteine quartile group and the cholesterol quartile group on cognitive scores (P=0

  18. Learn, how to learn

    Science.gov (United States)

    Narayanan, M.

    2002-12-01

    . Maintain Momentum. 13. Feedback : Communication. 14. Fact - Based Decisions. 15. Exploit Opportunities. 16. Mobilization of Expertise. 17. Drive out Fear. 18. Recognition / Keep Score. 19. Identify Accomplishments. 20. Customer Focus / Results. In conclusion, the author believes that the ACORN model and the QUOTES model may offer some guidelines that would help and enable the instructor to motivate learners to learn on their own. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate. Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., and Winter, J. (1997). Mastering change: Learning the lessons of the enterprise in higher education initiative. London: Department for Education and Employment. Narayanan, Mysore (2002). Total Quality Management (TQM) and the Teaching Professor. Oxford, Ohio. : Mimi University : 22nd Annual Lilly Conference on College Teaching.

  19. Variability in P-glycoprotein inhibitory potency (IC₅₀) using various in vitro experimental systems: implications for universal digoxin drug-drug interaction risk assessment decision criteria.

    Science.gov (United States)

    Bentz, Joe; O'Connor, Michael P; Bednarczyk, Dallas; Coleman, Joann; Lee, Caroline; Palm, Johan; Pak, Y Anne; Perloff, Elke S; Reyner, Eric; Balimane, Praveen; Brännström, Marie; Chu, Xiaoyan; Funk, Christoph; Guo, Ailan; Hanna, Imad; Herédi-Szabó, Krisztina; Hillgren, Kate; Li, Libin; Hollnack-Pusch, Evelyn; Jamei, Masoud; Lin, Xuena; Mason, Andrew K; Neuhoff, Sibylle; Patel, Aarti; Podila, Lalitha; Plise, Emile; Rajaraman, Ganesh; Salphati, Laurent; Sands, Eric; Taub, Mitchell E; Taur, Jan-Shiang; Weitz, Dietmar; Wortelboer, Heleen M; Xia, Cindy Q; Xiao, Guangqing; Yabut, Jocelyn; Yamagata, Tetsuo; Zhang, Lei; Ellens, Harma

    2013-07-01

    A P-glycoprotein (P-gp) IC₅₀ working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC₅₀ determinations. Each laboratory followed its in-house protocol to determine in vitro IC₅₀ values for 16 inhibitors using four different test systems: human colon adenocarcinoma cells (Caco-2; eleven laboratories), Madin-Darby canine kidney cells transfected with MDR1 cDNA (MDCKII-MDR1; six laboratories), and Lilly Laboratories Cells--Porcine Kidney Nr. 1 cells transfected with MDR1 cDNA (LLC-PK1-MDR1; four laboratories), and membrane vesicles containing human P-glycoprotein (P-gp; five laboratories). For cell models, various equations to calculate remaining transport activity (e.g., efflux ratio, unidirectional flux, net-secretory-flux) were also evaluated. The difference in IC₅₀ values for each of the inhibitors across all test systems and equations ranged from a minimum of 20- and 24-fold between lowest and highest IC₅₀ values for sertraline and isradipine, to a maximum of 407- and 796-fold for telmisartan and verapamil, respectively. For telmisartan and verapamil, variability was greatly influenced by data from one laboratory in each case. Excluding these two data sets brings the range in IC₅₀ values for telmisartan and verapamil down to 69- and 159-fold. The efflux ratio-based equation generally resulted in severalfold lower IC₅₀ values compared with unidirectional or net-secretory-flux equations. Statistical analysis indicated that variability in IC₅₀ values was mainly due to interlaboratory variability, rather than an implicit systematic difference between test systems. Potential reasons for variability are discussed and the simplest, most robust experimental design for P-gp IC₅₀ determination proposed. The impact of these findings on drug-drug interaction risk assessment is discussed in the companion article (Ellens

  20. Biopharma's Top R & D Spenders-2012%2012年国际生物制药研发前10名企业盘点

    Institute of Scientific and Technical Information of China (English)

    李明(译); 李新刚(审校)

    2013-01-01

      本文介绍了2012年研发支出在世界排名前10位的制药公司,将汇率因素计算在内,2012年这些公司的总研发费用达703.7亿美元,同比前一年的703.8亿美元有稍有下降。但是大多数公司,比如诺华,默克,强生,葛兰素史克,赛诺菲,礼来,阿斯利康和雅培的研发支出基本持平,只有辉瑞公司的支出大幅下降,而罗氏的一部分支出用在了大规模一次性重组上。AbbVie公司现在已经从雅培公司中拆分出来,形成了一个独立的生物制药企业。%The top-line R&D spending for the top 10 pharma companies was introduced. The gross research budgets for these companies hit $70.37 billion last year, down ever so slightly from $70.38 billion the year before, when viewed at constant exchange rates. But while most companies carefully stayed on an unchanged budget track--Novartis, Merck, J&J, GlaxoSmithKline, Sanofi, Eli Lilly, AstraZeneca and Abbott--Pfizer registered the big drop in spending that had long ago been forecast. Roche, meanwhile, saw its numbers jump in the face of some big, one-time restructuring costs. And Abbott is making an appearance for the last time as AbbVie has now spun out to forge its own unique path in the biopharma business.

  1. Probiotics

    Directory of Open Access Journals (Sweden)

    Gupta V

    2009-01-01

    Full Text Available The term "probiotic" was first used in 1965, by Lilly and Stillwell, to describe substances secreted by one organism which stimulate the growth of another. The use of antibiotics, immunosuppressive therapy and irradiation, amongst other means of treatment, may cause alterations in the composition and have an effect on the GIT flora. Therefore, the introduction of beneficial bacterial species to GI tract may be a very attractive option to re-establish the microbial equilibrium and prevent disease. Prebiotic is a non-digestible food ingredient that confers benefits on the host by selectively stimulating one bacterium or a group of bacteria in the colon with probiotic properties. Both probiotics and prebiotics are together called as Synbiotics. Various bacterial genera most commonly used in probiotic preparations are Lactobacillus, Bifidobacterium, Escherichia, Enterococcus, Bacillus and Streptococcus . Some fungal strains belonging to Saccharomyces have also been used. Probiotics have been shown to be effective in varied clinical conditions- ranging from infantile diarrhoea, necrotizing enterocolitis, antibiotic-associated diarrhoea, relapsing Clostridium difficle colitis, Helicobacter pylori infections, inflammatory bowel disease to cancer, female uro-genital infection and surgical infections. Lactobacillus rhamnosus strain GG has proven beneficial affects on intestinal immunity. It increases the number of IgA and other immunoglobulins secreting cells in the intestinal mucosa. It also stimulates local release of interferons. It facilitates antigen transport to underlying lymphoid cells, which serves to increase antigen uptake in Peyer′s patches. Probiotics are live microorganisms, so it is possible that they may result in infection in the host. The risk and morbidity of sepsis due to probiotic bacteria should be weighed against the potential for sepsis due to more pathological bacteria and the morbidity of diseases for which probiotic bacteria

  2. Residual symptoms in patients with partial versus complete remission of a major depressive disorder episode: patterns of painful physical symptoms in depression

    Directory of Open Access Journals (Sweden)

    Harada E

    2016-06-01

    Full Text Available Eiji Harada,1 Yoichi Satoi,2 Toshiaki Kikuchi,3 Koichiro Watanabe,3 Levent Alev,1 Masaru Mimura4 1Medical Science, Medicines Development Unit-Japan, 2Statistical Science, Medicines Development Unit-Japan, Eli Lilly Japan K.K., Kobe, Hyogo, 3Department of Neuropsychiatry, Kyorin University School of Medicine, 4Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan Objective: The patterns of residual painful physical symptoms (PPS and emotional symptoms among patients with partial remission (PR or complete remission (CR of a major depressive disorder (MDD episode were compared. Methods: This is a multicenter, cross-sectional, observational study. Patients who had originally been diagnosed with MDD, were treated with an antidepressant for 12 weeks for that episode, and achieved either PR or CR at study entry were enrolled in the study. Using the 17-item Hamilton Rating Scale for Depression (HAM-D17, PR was defined as a score of ≥8 and ≤18 and CR as a score of ≤7. Residual symptoms were assessed using the Brief Pain Inventory-Short Form (BPI-SF and the HAM-D17.Results: A total of 323 patients (CR =158, PR =165 were included in the study. Patients in the PR group had a higher mean (standard deviation score in the HAM-D17 than those in the CR group (11.8 [3.1] and 4.4 [2.0], respectively. BPI-SF results showed that “at least moderate PPS” (score ≥3 on BPI-SF question 5 was significantly more prevalent among patients with PR than those with CR (37.0% vs 16.5%, respectively; odds ratio =3.04; P<0.001. Presence of pain (any severity was also more prevalent among patients with PR than those with CR (54.5% vs 35.4%, respectively. The HAM-D17 results for individual items indicated that impaired work and activities, depressed mood, psychological and somatic anxiety, and general somatic symptoms were observed in at least 75% of patients with PR.Conclusion: PR was associated with a higher prevalence of at least moderate PPS

  3. The noradrenergic paradox: implications in the management of depression and anxiety

    Directory of Open Access Journals (Sweden)

    Montoya A

    2016-03-01

    Full Text Available Alonso Montoya,1 Robert Bruins,1 Martin A Katzman,2 Pierre Blier3 1Eli Lilly Canada Inc, 2START Clinic for the Mood and Anxiety Disorders, Toronto, 3Mood Disorders Research Unit, Institute of Mental Health Research, University of Ottawa, Ottawa, ON, Canada Abstract: Both major depressive disorder and the anxiety disorders are major causes of ­disability and markedly contribute to a significant global burden of the disease worldwide. In part because of the significant socioeconomic burden associated with these disorders, theories have been developed to specifically build clinical treatment approaches. One such theory, the monoaminergic hypothesis, has led to the development of several generations of selective and nonselective inhibitors of transporters of serotonin and norepinephrine, with the goal of augmenting monoaminergic transmission. These efforts have led to considerable success in the development of antidepressant therapeutics. However, there is a strong correlation between enhanced noradrenergic activity and fear and anxiety. Consequently, some physicians have expressed concerns that the same enhanced noradrenergic activity that alleviates depression could also promote anxiety. The fact that the serotonergic and noradrenergic reuptake inhibitors are successfully used in the treatment of anxiety and panic disorders seems paradoxical. This review was undertaken to determine if any clinical evidence exists to show that serotonergic and noradrenergic reuptake inhibitors can cause anxiety. The PubMed, EMBASE, and Cochrane Library databases were searched, and the results limited to randomized, double-blind, placebo-controlled studies performed in nongeriatric adults and with clear outcome measures were reported. Based on these criteria, a total of 52 studies were examined. Patients in these studies suffered from depression or anxiety disorders (generalized and social anxiety disorders, panic disorder, and posttraumatic stress disorder. The

  4. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

    Directory of Open Access Journals (Sweden)

    Jonathan González García

    2017-01-01

    Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

  5. Treatment progression in sulfonylurea and dipeptidyl peptidase-4-inhibitor cohorts of type 2 diabetes patients on metformin

    Directory of Open Access Journals (Sweden)

    Peng X

    2016-08-01

    Full Text Available Xiaomei Peng, Dingfeng Jiang, Dongju Liu, Oralee J Varnado, Jay P Bae Eli Lilly and Company, Global Patient Outcomes and Real World Evidence, Indianapolis, IN, USA Background: Metformin is an oral antidiabetic drug (OAD widely used as first-line therapy in type 2 diabetes (T2D treatments. Numerous treatment pathways after metformin failure exist. It is important to understand how treatment choices influence subsequent therapy progressions. This retrospective study compares adherence to, persistence with, and treatment progression in sulfonylurea (SU and dipeptidyl peptidase-4 (DPP-4 inhibitor patient cohorts with T2D on metformin. Methods: Using health insurance claims data, matched patient cohorts were created and OAD use was compared in patients with T2D initiating SU or DPP-4 inhibitors (index drugs since January 1, 2010, to December 31, 2010, with background metformin therapy. Propensity score matching adjusted for possible selection bias. Persistence was measured via Cox regression as days to a ≥60-day gap in index drug possession; adherence was defined as proportion of days covered (PDC ≥80%. Evolving treatment patterns were traced at 6-month intervals for 24 months following index drug discontinuation. Results: From among 19,621 and 7,484 patients in the SU and DPP-4 inhibitor cohorts, respectively, 6,758 patient pairs were matched. Persistence at 12 months in the SU cohort was 48.0% compared to 52.5% for the DPP-4 inhibitor cohort. PDC adherence (mean [SD] during the 12-month follow-up period was 63.3 (29.7 for the SU cohort and 65.5 (28.7 for the DPP-4 inhibitor cohort. PDC ≥80% was 40.5% and 43.4% in the SU and DPP-4 inhibitor cohorts, respectively. A higher percentage of patients in the SU cohort remained untreated. Following index drug discontinuation, monotherapy was more common in the SU cohort, while use of two or three OADs was more common in the DPP-4 inhibitor cohort. Insulin therapy initiation was higher in the SU

  6. Sisseminekuks : [luuletused] / Anna Haava ; [Impressioonid]: Viiu Härm

    Index Scriptorium Estoniae

    Haava, Anna, pseud., 1864-1957

    2004-01-01

    Sisu: Sisseminekuks ; Kartus ; Ööbikule ; Käokene, kuldalindu ; Mis sa tahad, kevade? ; Ei tule uni ; Hoia ennast; Tuksuv süda ; Sina oled kelm ; Hinge hellal' igatsusel' ; Kõik kallile ; Soov ; Unes nägin ; Võin ; Sinu silmad ; Sinu silmist pilk ; Kallis, sul on kuldne süda ; Sa kõige armsam mulle ; Oh võiksin ; Lill ; Nõmmelill ; Meie Mihkel ; Koidulale ; Ehitage rahukojad ; Emakeel ; Isamaja ; Väsinud ; Oh kuhu ma lähen? ; Ööbiku surm ; Ei saa mitte vaiki olla ; Ma olen näinud ; Südameta ; Sellepärast ; See oli ilusal õiekuul; Esimese lume ajal ; Mina vaat'sin muru pääle ; Ikka kurjalt sa mind vaatad ; Oh ma isegi ei tea ; Mis on luule paljalt sõnas? ; Oh oleksin ära surnud ; Lee ääres ; Sinu nimi ; Hoia vahest aken lahti ; Jumalaga jättes vaat'sid ; Ma laulan ; Ei oma õnne peita ; Küll oli ilus mu õieke ; Oh ära sa küsi ; Ei tule luule tuulest ; Köögis seisab ; Järv leegib eha paistel ; Sinu vanaema ; Nii ta on ; Tead küll, mu kuldkallis ; Ma lähen üle nõmme ; Lenda, lepatriinuke ; Vesi voolab, vesi kohab ; Üks ainus kord ; Oh kevade, oh õie-aeg ; Suur kontsert ; Kuupaistel ; Mets kohiseb ; Lind läks magama ; Kui sa tuled, too mull' lilli ; Sinilillekesed ; Ei ole sina minu ingel ; Ei mina õnne usu ; Viimast laulu ei saa laulda ; Kõige ilusam luule ; Üks on minul püham koda! ; Sa oled suurem kui su saatus ; Mu kodumaa, kus oled sa? ; Eest ära! ; Kui kandlekeeled katkevad ; Ma kõnnin koiduvalgel ; Mu mured kõik matsin ma maha ; Kui ma sulle armas olen ; Kas tahad tulla minuga? ; Sa vaata ette, süda! ; Truus sõpruses ma tahan ; Su silmade sügavuses ; Siis mine! ; See oli siis ; Mu süda usub ; Sind teretame, kuldapäike ; Mind jumalaga jätsid ; Sääl kord kasvab kaunis kodu ; Me oleme põhjamaa lapsed ; Hilised lilled ; Sa küsid, kus mu kodu ; külm ; Sina vaikiv, sügav öö ; Ju õitsvad kõik hellerheinad ; Öösünges kohab ; Kui saaks mullegi kord kodu ; On püha mulle mu kodumaa muld ; Oma hind vaid vaba

  7. Behaviours, thoughts and perceptions around mealtime insulin usage and wastage among people with type 1 and type 2 diabetes mellitus: A cross-sectional survey study.

    Science.gov (United States)

    Van Brunt, Kate; Pedersini, Riccardo; Rooney, Jillian; Corrigan, Sheila M

    2017-04-01

    People with diabetes who use mealtime insulin (MTI) were surveyed about insulin wastage and injection habits when insufficient insulin remains in a disposable prefilled pen/cartridge to administer a full dose in a single injection. Cross-sectional, online, self-reported survey of MTI usage/wastage behaviour in 400 adults with type 1 (n=120) or type 2 (n=280) diabetes mellitus administering >20units/day of MTI via 100units/ml prefilled pens/cartridges for ⩾1month, conducted in France, Germany, Italy and UK. Participants' mean±standard deviation age was 54.5±12.2years, body mass index was 29.9±7.2kg/m(2) and duration of MTI therapy was 8.6±7.8years. They administered 3.7±5.9 injections/day with meals, using 11.3±18.0 prefilled pens/cartridges per month. Overall, 63.5% split the dose across two prefilled pens/cartridges (i.e. administered two injections to obtain a full dose), 15.0% used just what remained in their current pen (i.e. took a lower-than-prescribed dose) and 36.3% discarded prefilled pens/cartridges still containing insulin (i.e. took full dose with new pen). The latter participants discarded a mean 5.5±8.2 prefilled pens/cartridges monthly still containing insulin, each containing 8.6±8.7 units of insulin. Participants who wasted insulin considered it frustrating, time-consuming and painful to inject twice. Patients taking >20units/day MTI can find transitions between insulin pens challenging. This study highlights the need to identify ways of improving transitions between pens to make transitions easier for insulin users, which could potentially improve adherence to prescribed doses and reduce waste. Copyright © 2016 Eli Lilly and Company. Published by Elsevier B.V. All rights reserved.

  8. DOW AGROSCIENCES TODAY AND NEW REVOLUTIONARY SOLUTIONS

    Directory of Open Access Journals (Sweden)

    Slavko Vujević

    2008-09-01

    Full Text Available Dow AgroSciences LLC, based in Indianapolis, Indiana, USA, is a top tier agricultural company providing innovative crop protection, pest and vegetation management, seed, and agricultural biotechnology solutions to serve the world's growing population. Global sales for Dow AgroSciences, a wholly owned subsidiary of The Dow Chemical Company, are $3.8 billion. The company's roots in the agricultural marketplace date back to 1950 as the agricultural unit of The Dow Chemical Company and as part of Eli Lilly and Company's agricultural business. In 1989, the DowElanco joint venture was formed, and the company continued to develop new products and acquire strategic businesses. DowElanco acquired majority ownership in Mycogen Seeds in 1996; in 1997, The Dow Chemical Company acquired 100 percent of DowElanco and the company was renamed Dow AgroSciences. Other significant acquisitions include acetochlor herbicide, Cargill Hybrid Seeds, several Brazilian seed companies and the agricultural chemicals business of Rohm and Haas. Dow AgroSciences is positioned for the future through focused implementation of its strategy which revolves around productivity, portfolio management and innovation. This focus allows the company to grow through an ambitious innovation program that maximizes the products being sold today and creates new, revolutionary solutions that will surprise customers in the future. D Dow AgroSciences is committed to sustainable chemistry and has a competitive advantage in our natural products discovery capability. We've won a prestigious award for technical innovation incorporating "green" chemistry principles into chemical design, manufacture and use. Dow AgroSciences offers a full range of seeds for corn, sunflowers, canola, cotton, soybeans and alfalfa. In addition, we have developed seeds specifically bred for nutritional quality. Dow AgroSciences uses conventional breeding techniques and tools of biotechnology to produce oils that are low in

  9. Long-acting injectable antipsychotics: focus on olanzapine pamoate

    Directory of Open Access Journals (Sweden)

    JP Lindenmayer

    2010-05-01

    Full Text Available JP LindenmayerDepartment of Psychiatry, New York University School of Medicine, New York NY, USAAbstract: Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS. While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of

  10. Diabetes mellitus and insulin in an aspirin sensitive asthmatic.

    Science.gov (United States)

    Caplin, I

    1976-03-01

    The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms

  11. Perceptions and impact of bipolar disorder in Japan: results of an Internet survey

    Directory of Open Access Journals (Sweden)

    Watanabe K

    2016-11-01

    Full Text Available Koichiro Watanabe,1 Eiji Harada,2 Takeshi Inoue,3 Yuka Tanji,2 Toshiaki Kikuchi1 1Department of Neuropsychiatry, Kyorin University, School of Medicine, Tokyo, 2Medical Science, Medicines Development Unit-Japan, Eli Lilly Japan KK, Hyogo, 3Department of Psychiatry, Tokyo Medical University, Tokyo, Japan Abstract: Bipolar disorder is a recurrent and episodic illness. This survey study assessed experiences and identified clinical insights of individuals with bipolar disorder. An Internet-based monitor system database was screened for patients with bipolar disorder in Japan (February and March 2013. Of 1,050 patients, 457 completed surveys, and results were analyzed with descriptive statistics. Approximately one-fourth of respondents were diagnosed with bipolar disorder on their first visit to medical institutions, although the most common initial diagnosis was depression/depressive state (65%. Mean time lag between first-time visit to a medical institution and receipt of correct diagnosis of bipolar disorder was 4 years; one-third of patients experienced more than 5 years of lag time. Three perceived reasons for lapsed time before correct diagnosis were “(patients Did not consider manic symptoms as illness, and did not tell the doctor about them,” “I (patient did not know of bipolar disorder,” and “Lack of communication between my doctor and myself (patient.” Among participants who believed that they were initially incorrectly diagnosed and improperly treated, most experienced socioeconomic problems, such as having long-term inability to work or to study (65%. Sources of encouragement for participants included “To have someone to consult with” (41% followed by having “People around me treat me the same as before” (40%. Individuals with bipolar disorder reported a time lag of many years before accurate diagnosis, and substantial burden imposed by the illness. Encouragement should be provided for individuals to live positively

  12. AMCP Partnership Forum: Driving Value and Outcomes in Oncology.

    Science.gov (United States)

    2017-05-01

    arrangements. Addressing these challenges could lead to improving cancer treatment. The AMCP Partnership Forum titled "Driving Value and Outcomes in Oncology" and the development of this report were supported by AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Foundation Medicine, IntrinsiQ Specialty Solutions, Janssen Oncology and Johnson and Johnson Health Systems, Eli Lilly and Company, National Pharmaceutical Council, Novartis Pharmaceuticals Corporation, Pharmaceutical Research and Manufacturers of America, Sanofi, Takeda Oncology, and Xcenda.

  13. The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States.

    Science.gov (United States)

    Thayer, Sarah; Bell, Christopher; McDonald, Craig M

    2017-06-01

    , PTC Therapeutics, Biomarin, and Catabasis on clinical trials regarding Duchenne muscular dystrophy clinical trial design, endpoint selection, and data analysis; Mitobridge for drug development; and Eli Lilly as part of a steering committee for clinical trials. Study concept and design were contributed primarily by Bell, along with Thayer and McDonald. Thayer collected the data, and data interpretation was performed by Thayer and Bell, along with McDonald. The manuscript was written by Thayer and Bell, along with McDonald, and revised by all the authors.

  14. Probiotics.

    Science.gov (United States)

    Gupta, V; Garg, R

    2009-01-01

    The term "probiotic" was first used in 1965, by Lilly and Stillwell, to describe substances secreted by one organism which stimulate the growth of another. The use of antibiotics, immunosuppressive therapy and irradiation, amongst other means of treatment, may cause alterations in the composition and have an effect on the GIT flora. Therefore, the introduction of beneficial bacterial species to GI tract may be a very attractive option to re-establish the microbial equilibrium and prevent disease. Prebiotic is a non-digestible food ingredient that confers benefits on the host by selectively stimulating one bacterium or a group of bacteria in the colon with probiotic properties. Both probiotics and prebiotics are together called as Synbiotics. Various bacterial genera most commonly used in probiotic preparations are Lactobacillus, Bifidobacterium, Escherichia, Enterococcus, Bacillus and Streptococcus . Some fungal strains belonging to Saccharomyces have also been used. Probiotics have been shown to be effective in varied clinical conditions- ranging from infantile diarrhoea, necrotizing enterocolitis, antibiotic-associated diarrhoea, relapsing Clostridium difficle colitis, Helicobacter pylori infections, inflammatory bowel disease to cancer, female uro-genital infection and surgical infections. Lactobacillus rhamnosus strain GG has proven beneficial affects on intestinal immunity. It increases the number of IgA and other immunoglobulins secreting cells in the intestinal mucosa. It also stimulates local release of interferons. It facilitates antigen transport to underlying lymphoid cells, which serves to increase antigen uptake in Peyer's patches. Probiotics are live microorganisms, so it is possible that they may result in infection in the host. The risk and morbidity of sepsis due to probiotic bacteria should be weighed against the potential for sepsis due to more pathological bacteria and the morbidity of diseases for which probiotic bacteria are being used as

  15. Especially for High School Teachers

    Science.gov (United States)

    Howell, J. Emory

    1999-07-01

    Secondary School Feature Articles * Super Science Connections, by Patricia B. McKean, p 916 * A pHorseshoe, by Roger Plumsky, p 935 National Conferences in Your Part of the Country For the past several months, considerable space in this column has been devoted to forthcoming national conferences and conventions and to highlights of conferences past. For some of us, location is fairly unimportant; but for most of us travel costs and time are both factors to consider when choosing a conference. The community of high school chemistry teachers is favored by the number of national conventions and conferences that are held each year in different locations. In 1999, for example, the spring National Meeting of the American Chemical Society was in Anaheim and the National Science Teachers Association National Convention was in Boston. This summer CHEMED '99 will be held in Fairfield, CT, August 1-5, and the fall National ACS Meeting will be in New Orleans. Teachers from the mid-South especially should consider attending the High School Program at New Orleans, described below by Lillie Tucker Akin, Chairperson of the Division's High School Program Committee. The event will be held on Sunday to minimize conflicts with the beginning of the school year. JCE at CHEMED '99 Stop by the JCE booth at CHEMED '99 in the exhibits area to learn more about the wide array of print and nonprint resources you can use in your classroom and laboratory. Members of the editorial staff will be on hand to talk with you. You are invited to participate in a workshop, "Promoting Active Learning through JCE Activity Sheets and Software", on Monday, August 1, 8:30-10:30. The free hands-on workshop is number WT11 and we encourage you to include it among your choices in the blanks provided on the third page of the registration form. We will also conduct an interactive session to listen to ideas for making the Journal more useful to you. Check the final program for location and time or inquire at the JCE

  16. Plant adaptive behaviour in hydrological models (Invited)

    Science.gov (United States)

    van der Ploeg, M. J.; Teuling, R.

    2013-12-01

    -224. [2] McClintock B. The significance of responses of the genome to challenge. Science 1984; 226: 792-801 [3] Ries G, Heller W, Puchta H, Sandermann H, Seldlitz HK, Hohn B. Elevated UV-B radiation reduces genome stability in plants. Nature 2000; 406: 98-101 [4] Lucht JM, Mauch-Mani B, Steiner H-Y, Metraux J-P, Ryals, J, Hohn B. Pathogen stress increases somatic recombination frequency in Arabidopsis. Nature Genet. 2002; 30: 311-314 [5] Kovalchuk I, Kovalchuk O, Kalck V., Boyko V, Filkowski J, Heinlein M, Hohn B. Pathogen-induced systemic plant signal triggers DNA rearrangements. Nature 2003; 423: 760-762 [6] Cullis C A. Mechanisms and control of rapid genomic changes in flax. Ann. Bot. (Lond.) 2005; 95: 201-206 [7] de Rosnay, P. and J. Polcher. 1998. Modelling root water uptake in a complex land surface scheme coupled to a GCM. Hydrology and Earth System Sciences 2: 239-255. [8] Feddes, R.A., H. Hoff, M. Bruen, T. Dawson, P. de Rosnay, P. Dirmeyer, R.B. Jackson, P. Kabat, A. Kleidon, A. Lilly, and A.J. Pitman. 2001. Modeling root water uptake in hydrological and climate models. Bulletin of the American Meteorological Society 82: 2797-2809. [9] Jung, M., M. Reichstein, P. Ciais, S.I. Seneviratne, J. Sheffield et al. 2010. Recent decline in the global land evaporation trend due to limited moisture supply. Nature 476: 951-954, doi:10.1038/nature09396.

  17. Writers, Athletes and Engineers Learn by Doing

    Science.gov (United States)

    Narayanan, M.

    2009-12-01

    provided evidence-based reasoning and critical thinking. 6. He/She has suggested a time-line for completing the assignment. 7. The person has completed the required process in the alloted time-line. In this presentation the author stresses the importance of writing assignments in engineering disciplines. References: Barr, R. B., & Tagg, J. (1995, November/December). From teaching to learning: A new paradigm for undergraduate education. Change: The Magazine of Higher Education, 13-24. Cox, M. D., Grasha, A., & Richlin, L. (1997, March). Town meeting. Between teaching model and learning model: Adapting and adopting bit by bit. Paper presented at the ninth annual Lilly Conference on College and University Teaching - West, Lake Arrowhead, CA. Narayanan, Mysore (2009). Assessment Based on the principles of Theodore Marchese. ASEE 116th Annual Conference and Exposition, Austin, TX. June 14-17, 2009. Paper # AC 2009-1532. Saxe, S. (1990, June). Peer influence and learning. Training and Development Journal, 42 (6), 50-53. Senge, P. M. (1990). The fifth discipline: The art and practice of the learning organization. New York: Currency Doubleday.

  18. Geochronology and geology of late Oligocene through Miocene volcanism and mineralization in the western San Juan Mountains, Colorado

    Science.gov (United States)

    Bove, D.J.; Hon, Ken; Budding, K.E.; Slack, J.F.; Snee, L.W.; Yeoman, R.A.

    2000-01-01

    Twenty-five new 40Ar/39Ar ages from volcanic rocks and veins in the western San Juan Mountains clarify relationships between volcanism and mineralization in this classic area. Five calc-alkaline ash-flow sheets erupted from caldera sources (Ute Ridge, Blue Mesa, Dillon Mesa, Sapinero Mesa, and Crystal Lake Tuffs) from 28.6 to 27.6 Ma. This is a much more restricted time interval than previously thought and indicates that the underlying batholith rose and evolved very rapidly beneath the western San Juan Mountains. The new ages and geologic relations constrain the timing of joint resurgence of the Uncompahgre and San Juan calderas to between 28.2 and 27.6 Ma. The collapse of the Silverton caldera produced a set of strong ring fractures that intersected with graben faults on the earlier resurgent dome to produce the complex set of structures that localized the mid-Miocene epithermal gold veins. Later calc-alkaline monzonitic to quartz monzontic plutons solidified at 26.5-26.0 Ma as the underlying batholith rose through its volcanic cover. A new age from lavas near Uncompahgre Peak supports earlier interpretations that these lavas were fed by nearby 26 Ma monzonite intrusions. Nearly all of these intrusions are associated with subeconomic Mo and Cu mineralization and associated alteration, and new ages of 26.40 and 25.29 Ma from the Ute-Ulay and Lilly veins in the Lake City region show that some of the most important silver and base-metal veins were temporally and possibly genetically connected to these plutons. In addition, the Golden Fleece telluride vein cuts all of the post-Uncompahgre caldera volcanics in the area and is probably temporally related to this cycle, though its age of 27.5 ? 0.3 Ma was determined by less precise U/Pb methods. The 22.9 Ma Lake City caldera collapsed within the older Uncompahgre caldera structure but is petrologically unrelated to the older calc-alkaline activity. The distinctive suite of high-silica rhyolite tuff and alkaline

  19. Comparison of numerical simulation methods for atmospheric pollutant dispersion under the effect of buildings%建筑物影响下大气污染物扩散数值模拟方法的比较

    Institute of Scientific and Technical Information of China (English)

    赵晓辉; 张宁; 李磊

    2013-01-01

    The effect of buildings on wind flow fields plays a very important role in air pollutant dispersion.Comparison and evaluation of different numerical simulation methods help improve the prediction on pollutant concentrations.Computational Fluid Dynamics (CFD) software FLUENT and the Gaussian model AERMOD were separately used to simulate pollutant concentration around a cube.FLUENT was run in the large eddy simulation (LES) mode,using the Smagorinsky-Lilly closure model,to resolve the larger scales of the flow field.AERMOD model based the classical Gaussian model developed by EPA and AMS considered building downwash.The numerical simulation results were compared with the wind tunnel experiment-Compilation of Experimental Data for Validation of microscale dispersion models (CEDVAL).The LES model can describe the pollutant dispersion characteristics well,and the simulation capability could be accepted in the whole simulation zone.The simulation capability of AERMOD model on pollutant concentration was poor compared with LES model,especially in the downwind recirculation cavity.The hypothesis of AERMOD model was compared with the numerical simulated results of the large eddy simulation model on wind speeds.It was shown that the simulation errors of AERMOD model on pollutant concentration were from the background wind flow fields.%利用计算流体力学软件Fluent6.3.26提供的大涡模式和国标推荐的AERMOD模式分别对方形建筑物影响下的大气污染物扩散进行了模拟,通过与风洞实验结果的比较,对各模式的模拟能力进行了评价.结果表明,大涡模式对污染物散布特征的模拟与风洞实验结果基本一致,对建筑物顶部、空腔区和尾流区等区域污染物浓度分布的模拟效果均处于可接受水平;AERMOD模式模拟结果与风洞试验结果偏离较远,尤其是对空腔区污染物散布的模拟能力较差,误差较大.与大涡模式Y/H =0平面流场模拟结果对比(H为建筑物高

  20. Classroom Assessment Techniques

    Science.gov (United States)

    Narayanan, M.

    2003-12-01

    and the learner should be carefully observed and monitored. Forrest says that Student Portfolios, which document learning in more detail, seldom reveal how teaching contributes to students' progress. Cerbin further indicates that a course portfolio is essentially, a like a manuscript of scholarly work in progress. In this example, it is a work that explains what, how, and why students learn or do not learn in a course. In this paper, the author reports on a dozen techniques that could perhaps be used to document assessment of student learning. References : Cerbin, W. (1993). Fostering a culture of teaching as scholarship. The Teaching Professor, 7(3), 1-2. Edgerton, R., Hutchings, P., & Quinlan, P. (1991). The teaching portfolio: Capturing the scholarship in teaching. Washington, DC: American Association for Higher Education. Forrest, A. (1990). Time will tell: Portfolio-assisted assessment of general education. Washington, DC: American Association for Higher Education. Linn, R., Baker, E., & Dunbar, S. (1991). Complex, Performance-based Assessment: Expectations and Validation Criteria. Educational Researcher, 20 (8), 15-21. Narayanan, M. (2003). Assessment in Higher Education: Partnerships in Learning. Paper presented at the 23rd Annual Lilly Conference on College Teaching, Miami University, Oxford, OH. Seldin, P. (1991). The teaching portfolio. Bolton, MA: Anker. Young, C. O., Sr., & Young, L. H. (1999). Assessing Learning in Interactive Courses. Journal on Excellence in College Teaching, 10 (1), 63-76.

  1. Large Eddy simulation of turbulence: A subgrid scale model including shear, vorticity, rotation, and buoyancy

    Science.gov (United States)

    Canuto, V. M.

    1994-01-01

    latter phenomenon, which affects both geophysical and astrophysical turbulence (e.g., oceanic structure and convective overshooting in stars), has been singularly difficult to account for in turbulence modeling. For example, the widely used model of Deardorff has not been confirmed by recent LES results. As of today, there is no SGS model capable of incorporating buoyancy, rotation, shear, anistropy, and stable stratification (gravity waves). In this paper, we construct such a model which we call CM (complete model). We also present a hierarchy of simpler algebraic models (called AM) of varying complexity. Finally, we present a set of models which are simplified even further (called SM), the simplest of which is the Smagorinsky-Lilly model. The incorporation of these models into the presently available LES codes should begin with the SM, to be followed by the AM and finally by the CM.

  2. Soil texture reclassification by an ensemble model

    Science.gov (United States)

    Cisty, Milan; Hlavcova, Kamila

    2015-04-01

    a prerequisite for solving some subsequent task, this bias is propagated to the subsequent modelling or other work. Therefore, for the sake of achieving more general and precise outputs while solving such tasks, the authors of the present paper are proposing a hybrid approach, which has the potential for obtaining improved results. Although the authors continue recommending the use of the mentioned parametric PSD models in the proposed methodology, the final prediction is made by an ensemble machine learning algorithm based on regression trees, the so-called Random Forest algorithm, which is built on top of the outputs of such models, which serves as an ensemble members. An improvement in precision was proved, and it is documented in the paper that the ensemble model worked better than any of its constituents. References Nemes, A., Wosten, J.H.M., Lilly, A., Voshaar, J.H.O.: Evaluation of different procedures to interpolate particle-size distributions to achieve compatibility within soil databases. Geoderma 90, 187- 202 (1999) Hwang, S.: Effect of texture on the performance of soil particle-size distribution models. Geoderma 123, 363-371 (2004) Botula, Y.D., Cornelis, W.M., Baert, G., Mafuka, P., Van Ranst, E.: Particle size distribution models for soils of the humid tropics. J Soils Sediments. 13, 686-698 (2013)

  3. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.

    Science.gov (United States)

    Petrylak, Daniel P; de Wit, Ronald; Chi, Kim N; Drakaki, Alexandra; Sternberg, Cora N; Nishiyama, Hiroyuki; Castellano, Daniel; Hussain, Syed; Fléchon, Aude; Bamias, Aristotelis; Yu, Evan Y; van der Heijden, Michiel S; Matsubara, Nobuaki; Alekseev, Boris; Necchi, Andrea; Géczi, Lajos; Ou, Yen-Chuan; Coskun, Hasan Senol; Su, Wen-Pin; Hegemann, Miriam; Percent, Ivor J; Lee, Jae-Lyun; Tucci, Marcello; Semenov, Andrey; Laestadius, Fredrik; Peer, Avivit; Tortora, Giampaolo; Safina, Sufia; Del Muro, Xavier Garcia; Rodriguez-Vida, Alejo; Cicin, Irfan; Harputluoglu, Hakan; Widau, Ryan C; Liepa, Astra M; Walgren, Richard A; Hamid, Oday; Zimmermann, Annamaria H; Bell-McGuinn, Katherine M; Powles, Thomas

    2017-09-12

    -2 severity. The frequency of grade 3 or worse adverse events was similar for patients allocated ramucirumab and placebo (156 [60%] of 258 vs 163 [62%] of 265 had an adverse event), with no unexpected toxic effects. 63 (24%) of 258 patients allocated ramucirumab and 54 (20%) of 265 assigned placebo had a serious adverse event that was judged by the investigator to be related to treatment. 38 (15%) of 258 patients allocated ramucirumab and 43 (16%) of 265 assigned placebo died on treatment or within 30 days of discontinuation, of which eight (3%) and five (2%) deaths were deemed related to treatment by the investigator. Sepsis was the most common adverse event leading to death on treatment (four [2%] vs none [0%]). One fatal event of neutropenic sepsis was reported in a patient allocated ramucirumab. To the best of our knowledge, ramucirumab plus docetaxel is the first regimen in a phase 3 study to show superior progression-free survival over chemotherapy in patients with platinum-refractory advanced urothelial carcinoma. These data validate inhibition of VEGFR-2 signalling as a potential new therapeutic treatment option for patients with urothelial carcinoma. Eli Lilly and Company. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. The need for good practices in biomedical technology.

    Science.gov (United States)

    Koech, D K

    1996-02-01

    issued Guidelines for Good Clinical Practice (GCP), Guidelines for Good Manufacturing Practices (GMP) of Pharmaceuticals, and Guidelines for the Production of Biologicals. It is thus evident that quality assurance is a very important aspect in all fields of health science research and practice. Quality assurance embraces quality control and audit and involves three things: personnel and material resources, quality system structure, and management responsibilities. Well trained personnel are required to use the appropriate materials and tools, an efficient quality system structure is desirable, and a good management system to implement the quality assurance programme is very essential. This programme should also enable the providers of goods and services to be bold enough to disclose to the consumers when their goods and services fail, as in the recent case of Abbot Laboratories when they had to withdraw their HIV test kit from the market after failing to meet the prescribed standards. Similarly, some years ago the anti-inflammatory drug Benoxaprofen (ORAFLEX-Eli Lilly) was withdrawn shortly after its introduction in the clinic. Do the organisations in Africa have the capacity to develop, or adopt, a quality assurance programme? It is fair to answer in the affirmative Organisations in Africa can, and should, adopt any of the existing quality assurance programmes that suit their operations best. What is most important is that operations must have the means to establish specificity, accuracy, precision and sensitivity that can be verified and certified. The big question is, do all these nicely worded standards, guidelines and practices have uniform and enforceable laws that enable their effective implementation and protection of the consumers?

  5. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.

    Science.gov (United States)

    Leder, Benjamin Z; Tsai, Joy N; Uihlein, Alexander V; Wallace, Paul M; Lee, Hang; Neer, Robert M; Burnett-Bowie, Sherri-Ann M

    2015-09-19

    from the DATA study, 77 completed at least one post-baseline visit. After 48 months, the primary outcome of mean spine bone mineral density increased by 18·3% (95% CI 14·9-21·8) in 27 women in the teriparatide to denosumab group, 14·0% (10·9-17·2) in 27 women the denosumab to teriparatide group, and 16·0% (14·0-18·0) in 23 women in the combination to denosumab group, although this increase did not differ significantly between groups (for between-group comparisons, p=0·13 for the teriparatide to denosumab group vs the denosumab to teriparatide group, p=0·30 for the teriparatide to denosumab group vs the combination to denosumab group, and p=0·41 for the denosumab to teriparatide group vs the combination to denosumab group). For the bone mineral density secondary outcomes, total hip bone mineral density increased more in the teriparatide to denosumab group (6·6% [95% CI 5·3-7·9]) than in the denosumab to teriparatide group (2·8% [1·3-4·2], p=0·0002), but had the greatest increase in the combination to denosumab group (8·6% [7·1-10·0]; p=0·0446 vs the teriparatide to denosumab group, ptransient bone loss. These results should be considered when choosing the initial and subsequent management of postmenopausal osteoporotic patients. Amgen, Eli Lilly, and National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Inhaled insulin--does it become reality?

    Science.gov (United States)

    Siekmeier, R; Scheuch, G

    2008-12-01

    , shortness of breath, sore throat and dry mouth. Physical exercise increases the transport of inhaled insulin into the circulation and in consequence the likelihood of hypoglycemia. Other problems were the inability to deliver precise insulin doses, because the smallest blister pack available contained the equivalent of 3 U of regular insulin and this dose would make it difficult for many people using insulin to achieve accurate control, which is the real goal of any insulin therapy. For example, someone on 60 U of insulin per day would lower the blood glucose about 90 mg/dl (5 mmol) per 3 U pack, while someone on 30 U a day would drop 180 mg/dl (10 mmol) per pack. Precise control was not possible, especially compared with an insulin pump that can deliver one twentieth of a unit with precision. Another disadvantage was the size of the device. The Exubera inhaler, when closed, was about the size of a 200 ml water glass. It opened to about twice the size for delivery. To our information also other companies (Eli Lilly in cooperation with ALKERMES, Novo Nordisk (AERx, Liquid), Andaris (Powder)) stopped further development and it is unclear whether an inhaled form of insulin will ever be marketed, because of the problems that have occurred. Only Mannkind (Technosphere, Powder) is still working on a Phase III trial. However, our review will briefly summarize the experience regarding inhalant administration of insulin and will describe potential future developments for this type of therapy focussing on the lung.

  7. Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis

    Directory of Open Access Journals (Sweden)

    Gaebler JA

    2012-04-01

    Full Text Available Julia A Gaebler1, Gerardo Soto-Campos2, Peter Alperin2, Marc Cohen2, Amy Blickensderfer1, Matthew Wintle1, David Maggs1, Byron Hoogwerf3, Jenny Han1, Richard Pencek1, Barbara Peskin21Amylin Pharmaceuticals, Inc, San Diego CA, 2Archimedes Inc, San Francisco CA, 3Eli Lilly and Company, Indianapolis, IN, USABackground: Patients with type 2 diabetes (T2DM are at risk of long-term vascular complications. In trials, exenatide once weekly (ExQW, a GLP-1R agonist, improved glycemia, weight, blood pressure (BP, and lipids in patients with T2DM. We simulated potential effects of ExQW on vascular complications, survival, and medical costs over 20 years versus standard therapies.Patients and methods: The Archimedes model was used to assess outcomes for ~25,000 virtual patients with T2DM (NHANES 1999–2006 [metformin ± sulfonylureas, age 57 years, body mass index 33 kg/m2, weight 94 kg, duration T2DM 9 years, hemoglobin A1c [A1C] 8.1%]. The effects of three treatment strategies were modeled and compared to moderate-adherence insulin therapy: advancement to high-adherence insulin at A1C ≥ 8% (treat to target A1C < 7% and addition of pioglitazone (PIO or ExQW from simulation start. ExQW effects on A1C, weight, BP, and lipids were modeled from clinical trial data. Costs, inflated to represent 2010 $US, were derived from Medicare data, Drugstore.com, and publications. As ExQW was investigational, we omitted ExQW, PIO, and insulin pharmacy costs.Results: By year 1, ExQW treatment decreased A1C (~1.5%, weight (~2 kg, and systolic BP (~5 mmHg. PIO and high-adherence insulin decreased A1C by ~1%, increased weight, and did not affect systolic BP. After 20 years, A1C was ~7% with all strategies. ExQW decreased rates of cardiovascular and microvascular complications more than PIO or high-adherence insulin versus moderate-adherence insulin. Over 20 years, ExQW treatment resulted in increased quality-adjusted life-years (QALYs of ~0.3 years/person and cost savings of

  8. Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell lung cancer in Spain.

    Science.gov (United States)

    González García, Jonathan; Gutiérrez Nicolás, Fernando; Nazco Casariego, Gloria Julia; Valcárcel Nazco, Cristina; Batista López, Jose Norberto; Oramas Rodríguez, Juana

    2017-01-01

    Introducción: El cáncer de pulmón es la tercera neoplasia tumoral más frecuente en España, con unos 27.000 nuevos casos/ año, de los que el 80-85% son de etiología no microcítica (NSCLC) y en la mayoría de los casos diagnosticados en estadíos avanzados de la enfermedad, razón por la que es uno de los procesos oncológicos con mayores tasas de mortalidad (supervivencia media a los 5 años del 21,4%). Los principales esquemas de primera línea utilizados en el tratamiento del NSCLC son: cisplatino/pemetrexed (cis/pem), cisplatino/gemcitabina/ bevacizumab (cis/gem/bev), y carboplatino/paclitaxel/bevacizumab (carbo/pac/Bev). El objetivo del presente trabajo consistirá en realizar un análisis para estimar el ratio coste-eficacia de los esquemas antineoplásicos de primera línea en el tratamiento del NSCLC, desde la perspectiva de la gerencia hospitalaria. Metodos: Se elaboró un modelo matemático de coste-eficacia basado en un árbol de decisiones. Como variable de eficacia se utilizó la supervivencia libre de progresión, obtenida de los ensayos clínicos fase III PARAMOUNT, AVAIL y SAIL. El estudio se efectuó desde la perspectiva de la gerencia hospitalaria considerando únicamente los costes directos de adquisición de los fármacos. Se realizó un análisis de sensibilidad determinístico para comprobar la robustez de los resultados. Resultados: La SLP obtenida en los ensayos clínicos de los tratamientos cis/pem, cis/gem/bev y carb/pac/bev fue de: 6,9, 6,7 y 6,2 meses, respectivamente. En base a nuestro modelo, el coste medio del tratamiento por paciente para estos esquemas fue de 19.942 €, 15.594 € y 36.095 €, respectivamente. La razón coste-eficacia incremenal por mes de SLP adicional entre cis/pem y cis/gem/bev fue de 19.303 €. Estimando una reducción del 30% de los costes de adquisición de pemetrexed (Alimta®Eli Lilly Nederland B.V) ante su próxima incorporación al mercado de medicamentos genéricos, el tratamiento cis/pem se

  9. Do new cancer drugs offer good value for money? The perspectives of oncologists, health care policy makers, patients, and the general population

    Directory of Open Access Journals (Sweden)

    Dilla T

    2015-12-01

    Full Text Available Tatiana Dilla,1 Luís Lizan,2 Silvia Paz,2 Pilar Garrido,3 Cristina Avendaño,4 Juan J Cruz-Hernández,5 Javier Espinosa,6 José A Sacristán1 1Medical Department, Lilly, Madrid, 2Outcomes’10, Jaime I University, Castellón, 3Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, 4Clinical Pharmacology Department, Puerta de Hierro-Majadahonda Hospital, Madrid, 5Salamanca Institute for Biomedical Research, University Hospital of Salamanca, Salamanca, 6Medical Oncology Department, General Hospital Ciudad Real, Ciudad Real, Spain Background: In oncology, establishing the value of new cancer treatments is challenging. A clear definition of the different perspectives regarding the drivers of innovation in oncology is required to enable new cancer treatments to be properly rewarded for the value they create. The aim of this study was to analyze the views of oncologists, health care policy makers, patients, and the general population regarding the value of new cancer treatments. Methods: An exploratory and qualitative study was conducted through structured interviews to assess participants’ attitudes toward cost and outcomes of cancer drugs. First, the participants were asked to indicate the minimum survival benefit that a new treatment should have to be funded by the Spanish National Health System (NHS. Second, the participants were requested to state the highest cost that the NHS could afford for a medication that increases a patient’s quality of life (QoL by twofold with no changes in survival. The responses were used to calculate incremental cost-effectiveness ratios (ICERs. Results: The minimum improvement in patient survival means that justified inclusions into the NHS were 5.7, 8.2, 9.1, and 10.4 months, which implied different ICERs for oncologists (€106,000/quality-adjusted life year [QALY], patients (€73,520/QALY, the general population (€66,074/QALY, and health care policy makers (€57,471/QALY, respectively

  10. Connecting research discovery with care delivery in dementia: the development of the Indianapolis Discovery Network for Dementia

    Directory of Open Access Journals (Sweden)

    Boustani MA

    2012-11-01

    Full Text Available Malaz A Boustani,1–3 Amie Frame,1,2 Stephanie Munger,1,2 Patrick Healey,4 Jessie Westlund,5 Martin Farlow,6,7 Ann Hake,8 Mary Guerriero Austrom,6,9 Polly Shepard,10 Corby Bubp,10 Jose Azar,3 Arif Nazir,3 Nadia Adams,11 Noll L Campbell,1,2,12,13 Azita Chehresa,5 Paul Dexter2,31Indiana University Center for Aging Research, 2Regenstrief Institute, Inc, 3Department of Medicine, Indiana University School of Medicine (IUSM, 4St Vincent Health Network, 5Community Health Network, 6Indiana Alzheimer Disease Center, IUSM, 7Department of Neurology, IUSM, 8Eli Lilly and Company, 9Department of Psychiatry, IUSM, 10The Memory Clinic of Indianapolis, 11Indiana University Health, Indianapolis, IN, USA; 12Department of Pharmacy Practice, Purdue University College of Pharmacy, West Lafayette, IN, USA; 13Department of Pharmacy, Wishard Health Services, Indianapolis, IN, USABackground: The US Institute of Medicine has recommended an integrated, locally sensitive collaboration among the various members of the community, health care systems, and research organizations to improve dementia care and dementia research.Methods: Using complex adaptive system theory and reflective adaptive process, we developed a professional network called the “Indianapolis Discovery Network for Dementia” (IDND. The IDND facilitates effective and sustainable interactions among a local and diverse group of dementia researchers, clinical providers, and community advocates interested in improving care for dementia patients in Indianapolis, Indiana.Results: The IDND was established in February 2006 and now includes more than 250 members from more than 30 local (central Indiana organizations representing 20 disciplines. The network uses two types of communication to connect its members. The first is a 2-hour face-to-face bimonthly meeting open to all members. The second is a web-based resource center (http://www.indydiscoverynetwork.org. To date, the network has: (1 accomplished the

  11. Spectral Gap Energy Transfer in Atmospheric Boundary Layer

    Science.gov (United States)

    Bhushan, S.; Walters, K.; Barros, A. P.; Nogueira, M.

    2012-12-01

    Experimental measurements of atmospheric turbulence energy spectra show E(k) ~ k-3 slopes at synoptic scales (~ 600 km - 2000 km) and k-5/3 slopes at the mesoscales (transfer, energy arrest at macroscales must be introduced. The most commonly used turbulence models developed to mimic the above energy transfer include the energy backscatter model for 2D turbulence in the horizontal plane via Large Eddy Simulation (LES) models, dissipative URANS models in the vertical plane, and Ekman friction for the energy arrest. One of the controversial issues surrounding the atmospheric turbulence spectra is the explanation of the generation of the 2D and 3D spectra and transition between them, for energy injection at the synoptic scales. Lilly (1989) proposed that the existence of 2D and 3D spectra can only be explained by the presence of an additional energy injection in the meso-scale region. A second issue is related to the observations of dual peak spectra with small variance in meso-scale, suggesting that the energy transfer occurs across a spectral gap (Van Der Hoven, 1957). Several studies have confirmed the spectral gap for the meso-scale circulations, and have suggested that they are enhanced by smaller scale vertical convection rather than by the synoptic scales. Further, the widely accepted energy arrest mechanism by boundary layer friction is closely related to the spectral gap transfer. This study proposes an energy transfer mechanism for atmospheric turbulence with synoptic scale injection, wherein the generation of 2D and 3D spectra is explained using spectral gap energy transfer. The existence of the spectral gap energy transfer is validated by performing LES for the interaction of large scale circulation with a wall, and studying the evolution of the energy spectra both near to and far from the wall. Simulations are also performed using the Advanced Weather and Research Forecasting (WRF-ARW) for moist zonal flow over Gaussian ridge, and the energy spectra close

  12. Economic Impact of Above-Label Dosing with Etanercept, Adalimumab, or Ustekinumab in Patients with Psoriasis.

    Science.gov (United States)

    Feldman, Steven R; Zhao, Yang; Zhou, Huanxue; Herrera, Vivian; Tian, Haijun; Li, Yunfeng

    2017-05-01

    above-label use were $19,458 for etanercept, $18,972 for adalimumab, and $21,045 for ustekinumab. Total additional annual costs were $5,623,362 for etanercept, $701,964 for adalimumab, and $1,304,790 for ustekinumab. Psoriasis patients treated with etanercept, adalimumab, or ustekinumab had extensive above-label use over the 12-month follow-up period, which subsequently led to higher costs. Novartis Pharmaceuticals Corporation sponsored this study and the resultant publication. BioScience Communications provided medical writing and editorial support, which was also funded by Novartis Pharmaceuticals Corporation. Feldman was engaged by Novartis Pharmaceuticals as a paid clinical expert and scientific advisor for this study. He has received research support and speaking and/or consulting fees from AbbVie, Advance Medical, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Caremark, Celgene, Eli Lilly, Galderma, GSK/Stiefel, Informa, Janssen, LEO Pharma, Merck, Merz, Mylan, National Biological, National Psoriasis Foundation, Pfizer, Qurient, Suncare Research, UpToDate, and Valeant; is the founder and majority owner of www.DrScore.com ; and is founder and part owner of Causa Research. Zhao, Herrera, Tian, and Li are employees of Novartis Pharmaceuticals. Zhou is a paid consultant for Novartis Pharmaceuticals and is an employee of KMK Consulting. Study concept and design were contributed by Feldman, Zhao, Herrera, and Li. Zhou and Li were responsible for data collection. Data were interpreted by Feldman and Zhao, with assistance from Zhou, Herrera, Tian, and Li. The manuscript was written primarily by Feldman and Zhao, with assistance from Zhou and Li. The manuscript was revised by Feldman and Zhao, assisted by Zhou, Herrera, Tian, and Li. Portions of this work were presented at the 34th Anniversary Fall Clinical Dermatology Conference in Las Vegas, Nevada, October 1-4, 2015.

  13. Geologic map of the Frisco quadrangle, Summit County, Colorado

    Science.gov (United States)

    Kellogg, Karl S.; Bartos, Paul J.; Williams, Cindy L.

    2002-01-01

    : Contributions to Mineralogy and Petrology, v. 67, p. 379-396.). Surficial deposits include (1) an old, deeply dissected landslide deposit, possibly as old as Tertiary, on the south flank of Tenderfoot Mountain, (2) deeply weathered, very coarse gravel deposits, mostly along Gold Run and underlying Mesa Cortina; the gravels are gold bearing and were mined by hydraulic methods in the 1800's, (3) glacial deposits of both Bull Lake (middle Pleistocene) and Pinedale (late Pleistocene) that were derived from large valley glaciers that flowed down Tenmile and North Tenmile Creeks; the town of Frisco is underlain mostly by Pinedale-age glacial outwash, (4) recent landslide deposits, including one large (about 1 square kilometer) area just downslope from Lilly Pad Lake, west of I-70, and (5)extensive colluvial and alluvial deposits. The latest seismic events appear to be middle Pliestocene in age and are associated with small scarps that cut Bull Lake till but do not cut Pinedale till.

  14. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial.

    Science.gov (United States)

    Thatcher, Nick; Hirsch, Fred R; Luft, Alexander V; Szczesna, Aleksandra; Ciuleanu, Tudor E; Dediu, Mircea; Ramlau, Rodryg; Galiulin, Rinat K; Bálint, Beatrix; Losonczy, György; Kazarnowicz, Andrzej; Park, Keunchil; Schumann, Christian; Reck, Martin; Depenbrock, Henrik; Nanda, Shivani; Kruljac-Letunic, Anamarija; Kurek, Raffael; Paz-Ares, Luis; Socinski, Mark A

    2015-07-01

    and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11·5 months [95% CI 10·4-12·6]) vs 9·9 months [8·9-11·1]; stratified hazard ratio 0·84 [95% CI 0·74-0·96; p=0·01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3-4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [<1%]). Including events related to disease progression, adverse events with an outcome of death were reported for 66 (12%) of 538 patients in the necitumumab plus gemcitabine and cisplatin group and 57 (11%) of 541 patients in the gemcitabine and cisplatin group; these were deemed to be related to study drugs in 15 (3%) and ten (2%) patients, respectively. Overall, we found that the safety profile of necitumumab plus gemcitabine and cisplatin was acceptable and in line with expectations. Our findings show that the addition of necitumumab to gemcitabine and cisplatin chemotherapy improves overall survival in patients with advanced squamous non-small-cell lung cancer and represents a new first-line treatment option for this disease. Eli Lilly and Company. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. EDITORIAL: Modelling and simulation in polymer and composites processing

    Science.gov (United States)

    Castro, Josè M.

    2004-05-01

    compromises. The exergy approach used by Srinivasagupta and Kardos to evaluate the ecological impact has shown great potential for measuring the effect of processes in the environment. The process they discuss is an environmentally friendly alternative to the standard pultrusion process. The sixth paper, by Chensong Dong and collaborators, focuses on modelling and optimizing dimensional variation in composites, and offers a good complement to Advani's papers. Papers seven by Lilly et al, and eight by Lyytikainen et al, focus on thermoplastic moulding. The last paper, by Chen et al, discusses the modelling of a technology that has the potential to be the environmentally friendly alternative to painting. I would like to thank Dr Mauricio Cabrera Rios, who obtained his PhD under my supervision and is now a professor at the Universidad Autonoma de Nuevo Leon, Mexico, for his help in coordinating the paper reviews. Also, the willingness of the authors to go through several review iterations where needed is greatly appreciated. Finally I would like to thank Ms Judith Adams (editor), without whose help this issue would not have been possible. She was instrumental in securing some papers and in obtaining the proper evaluations of others.

  16. Autoportree : [luuletused] / Artur Alliksaar ; [Impressioonid] : Viiu Härm

    Index Scriptorium Estoniae

    Alliksaar, Artur, 1923-1966

    2004-01-01

    Sisu: Autoportree ; Antidolorosum ; Asüül ; Sententse kahesusest (Nefas) ; Üksinduse randadel ; Ootus ; Uskumus ; Pilgud punuvad püüniseid ; Selgimus ; Talveidüll ; Tantsijad ; Sõnade sügis ; Optimistlik eleegia ; Jällenägemine (Quasi una fantasia) ; Kolm unesoolot kuuldamatu kooriga ; Padrikus ; Tundmatu eel ; Õnnelähistel ; Nauding ; Hilissuve päev ; Neis mälestustes pole kahetsust ; Mu hinges mälestused on tõusnud troonile ; Laskumine ; Ahtumine ; Üks sügishommik on äkki vilu... ; Hea oleks teada... ; Salapärane rongkäik ; Janud ; Seitse etüüdi ; Nõiaringis ; Kahe ääretuse vahel...; Õhtu rannas ; Keegi ei tea... (Primitiive) ; Eelärkamine ; Kirjaneitsi mälestuseks ; Friedebert Tuglasele ; Rein Sepale ; Mõttejoomar ; Kolm kunstnikku: Altamira Nimetu ; Vabadus ; Navigaatorid ; Ei hävi mõte, varjav elu seemneid ; Olematus võiks ju ka olemata olla ; Alternatiive ; Ärev on ärkamine äikesesse ; Nokturn, veidi ärev ja veidi kurb ; Ootesaalis ; Päikestepillajad ; Eleegiline ditüramb dialektilise analüüsi elementidega ; Sain siledaks vileda vile, mille kõikainsa aine ja helilained pühendan Ain Kaalepile ; "Santa Maria" ; Ulmfantaasiaid ; Tule, kuula, kuidas kumisevad uned ; Kamalutäis kaaluvihte ; On see õitsvate kaktuste sosin? (Picasso - Magnelli - Mir̤) ; Mis kuulub kõigile, ei kuulu kellelegi ; Tuulefuuga tumma suuga mõtisklusse vajund puuga... ; Välkvisioon ; Kohtumisi ; Lahkühtimine ; Avastusretk ; Lootust peab pälvima ; Kahekesi ; Liturgiline litsents ; Käidi ja külvati varjude seemneid, sest valgus hakkas võrsuma ; Tule, tule tulega! ; Kuigi on nii palju lilli... ; Pöördehetk ; Küsin sinult... ; Armastuse teed on voolavad kui veed ; Sidruniballaad ; Katkeid ; On asju, milles eksida ei saa ; Diletandi mõtteid vabavärsist ; Teeme hüppe laanerüppe kevadmaikudes, iga viga, haigus vaibub vaiguvaikuses (valimik mikrovalme) ; Lüüriline intermetso ; Jagamatu on jagatud ; Välgud peeglis ; Nostalgia ; Tikut

  17. Autoportree : [luuletused] / Artur Alliksaar ; [Impressioonid] : Viiu Härm

    Index Scriptorium Estoniae

    Alliksaar, Artur, 1923-1966

    2004-01-01

    Sisu: Autoportree ; Antidolorosum ; Asüül ; Sententse kahesusest (Nefas) ; Üksinduse randadel ; Ootus ; Uskumus ; Pilgud punuvad püüniseid ; Selgimus ; Talveidüll ; Tantsijad ; Sõnade sügis ; Optimistlik eleegia ; Jällenägemine (Quasi una fantasia) ; Kolm unesoolot kuuldamatu kooriga ; Padrikus ; Tundmatu eel ; Õnnelähistel ; Nauding ; Hilissuve päev ; Neis mälestustes pole kahetsust ; Mu hinges mälestused on tõusnud troonile ; Laskumine ; Ahtumine ; Üks sügishommik on äkki vilu... ; Hea oleks teada... ; Salapärane rongkäik ; Janud ; Seitse etüüdi ; Nõiaringis ; Kahe ääretuse vahel...; Õhtu rannas ; Keegi ei tea... (Primitiive) ; Eelärkamine ; Kirjaneitsi mälestuseks ; Friedebert Tuglasele ; Rein Sepale ; Mõttejoomar ; Kolm kunstnikku: Altamira Nimetu ; Vabadus ; Navigaatorid ; Ei hävi mõte, varjav elu seemneid ; Olematus võiks ju ka olemata olla ; Alternatiive ; Ärev on ärkamine äikesesse ; Nokturn, veidi ärev ja veidi kurb ; Ootesaalis ; Päikestepillajad ; Eleegiline ditüramb dialektilise analüüsi elementidega ; Sain siledaks vileda vile, mille kõikainsa aine ja helilained pühendan Ain Kaalepile ; "Santa Maria" ; Ulmfantaasiaid ; Tule, kuula, kuidas kumisevad uned ; Kamalutäis kaaluvihte ; On see õitsvate kaktuste sosin? (Picasso - Magnelli - Mir̤) ; Mis kuulub kõigile, ei kuulu kellelegi ; Tuulefuuga tumma suuga mõtisklusse vajund puuga... ; Välkvisioon ; Kohtumisi ; Lahkühtimine ; Avastusretk ; Lootust peab pälvima ; Kahekesi ; Liturgiline litsents ; Käidi ja külvati varjude seemneid, sest valgus hakkas võrsuma ; Tule, tule tulega! ; Kuigi on nii palju lilli... ; Pöördehetk ; Küsin sinult... ; Armastuse teed on voolavad kui veed ; Sidruniballaad ; Katkeid ; On asju, milles eksida ei saa ; Diletandi mõtteid vabavärsist ; Teeme hüppe laanerüppe kevadmaikudes, iga viga, haigus vaibub vaiguvaikuses (valimik mikrovalme) ; Lüüriline intermetso ; Jagamatu on jagatud ; Välgud peeglis ; Nostalgia ; Tikut

  18. Importance of Technical Writing in Engineering Education

    Science.gov (United States)

    Narayanan, M.

    2010-12-01

    ., Grasha, A., & Richlin, L. (1997, March). Town meeting. Between teaching model and learning model: Adapting and adopting bit by bit. Paper presented at the ninth annual Lilly Conference on College and University Teaching - West, Lake Arrowhead, CA. Narayanan, Mysore (2009). Assessment Based on the principles of Theodore Marchese. ASEE 116th Annual Conference and Exposition, Austin, TX. June 14-17, 2009. Paper # AC 2009-1532. Saxe, S. (1990, June). Peer influence and learning. Training and Development Journal, 42 (6), 50-53. Senge, P. M. (1990). The fifth discipline: The art and practice of the learning organization. New York: Currency Doubleday. Sims, R. R. (1992, Fall). Developing the learning climate in public sector training programs. Public Personnel Management, 21 (3), 335-346. Kosakowski, John, (1998). The Benefits of Information Technology. ERIC Digests; Technology Integration; Technology Role, ED0-IR-98-04 Chaika, Gloria (2000), Encourage Student Writing: Published on the Web, Education World http://www.education-world.com/a_tech/tech042.shtml

  19. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Science.gov (United States)

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    The development and progress of antidiabetic drugs (e.g., insulin preparations and hypoglycemic drugs) are retrospectively investigated in Japan. Their influences on the treatment of diabetes mellitus (DM) and its epidemiological aspects are also discussed. 1) Insulin preparations: Insulin was introduced for DM therapy in 1925, two or three years after its discovery in Canada. The preparations were raw extracts of bovine or porcine pancreas. These did not prevail widely in Japan because of the low incidence of DM before World Wan II. After the war, a shortage of mammalian materials compelled the use of fish pancreatic tissues such as bonito and/or tuna for insulin production. Insulin infection, so-called regular insulin, was first promoted in the 6th "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present edition (JP14, 2001). Although depot-type insulin preparations were developed in the USA and Europe during the war, the introduction of those preparations to Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc insulin and Isophane insulin were introduced for clinical use in 1952 and 1955, respectively. These were also adopted for JP7 (1961). Biphasic-type insulin, which has a rapid onset and long duration of activity, appeared in 1965. Purified preparations from bovine or porcine sources have been available since 1980, which might be a strong reason for the decrease in insulin allergy. Insulin from animal origin has been supplied for almost 60 years since its discovery. Amino acid sequences of insulins from various species of animals were determined by the pioneering studies of Sanger and his associates. Human insulin, which differs from porcine insulin by only one amino acid, was produced by Novo researchers in 1982 using a semi-synthetic method. Then the Lilly group soon succeeded in obtaining human insulin by recombinant DNA technology in the same year. Both products were introduced to Japan in 1985, and the

  20. Laps(epõlv 19. sajandi teise poole Eestis omaelulooliste tekstide näitel. Child(hood in 19th Century Estonia: a Study of Autobiographical Texts

    Directory of Open Access Journals (Sweden)

    Ave Mattheus

    2012-04-01

    Full Text Available In this article I discuss autobiographical texts which focus on children and childhood in late 19th century Estonia. Childhood memories as well as other autobiographical material became popular in Estonia in the 1920s-1930s, when most of the studied works--the memoirs by Anna Haava, Mait Metsanurk, Jaan Lattik, Jaan Vahtra, Friedebert Tuglas, August Kitzberg and Marta Sillaots--were written. Some texts come from the 19th century (e.g. Lilli Suburg’s autobiographical works or early 20th century (e.g. manuscripts by Hans Leoke, and Johannes Kõrv. Childhood as described in these autobiographical texts covers a period of circa 1850-1900, and the majority of the authors come from the families of South-Estonian peasants or manorial servants. In addition to being written in Estonian and having the same theme, they were all also written by authors of fiction for children or by people who had close contact with children, such as schoolteachers. The article offers a novel approach in the Estonian context by presenting a typology of childhood stories and looking at childhood recollections as an important part of childhood studies. The researchers of childhood investigate how society understands and values children and childhood, what children’s everyday life is like, what possibilities there are for development and if there exists a specific children’s culture in society (such as clothing, food, language, leisure activities, or independent creative work. Childhood studies as a separate discipline does not exist in Estonia, although some important works have been published by educational scholars and art historians. The autobiographical texts under discussion show that in the late 19th century, the majority of Estonian children lived in the countryside in patriarchal families, and childhood was short because children had to help their parents with farmwork quite early, at the age of six. The boundary of childhood was around the age of 10-11, when

  1. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    -signaling proteins in pollen tubes from the lilly Agapanthus umbellatus. For the uptake of DNA pollen tubes represent a unique system since the growing tip is surrounded by a loose matrix of hemicellulose and pectins, exposing the plasma membrane7 and the first uptake of ODNs by pollen tubes was reported as early as 1994. A breakthrough in the employment of antisense ODN inhibition as a powerful approach in plant biology was recently presented through our work on intact barley leaves. As was illustrated by confocal microscopy and fluorescently labeled ODNs, naked ODNs were taken up through the leaf petiole and efficiently imported into the plant cell and the nucleus. The work portrayed in that study demonstrate the applicability of antisense ODN inhibition in plant biology, e.g. as a rapid antecedent to time-consuming transgenic studies, and that it operates through RNase H degradation. We employed the antisense ODN strategy to demonstrate the importance of the SUSIBA2 transcription factor in regulation of starch synthesis, and to depict a possible mechanism for sugar signaling in plants and how it might confer endosperm-specific gene expression during seed development. We also described the employment of the antisense ODN strategy for studies on in vitro spike cultures of barley. Here we present further evidence as to the value of the antisense ODN approach in plant biology by following the effects on starch branching enzyme (SBE) accumulation in barley leaves after suppression of individual SBE genes. In agreement with transcript analyses of SBE expression in barley leaves, a zymogram assay (Fig. 1) revealed that sucrose treatment of barley leaves increased the number of SBE activity bands as compared to sorbitol treatment. In the presence of antisense SBEI or SBEIIA ODNs, zymograms of sucrose-treated leaves displayed only a subset of these activities with bands in the top portion of the zymogram gel missing or diminished. With antisense SBEIIB ODN, all activity bands in the top

  2. Antisense oligodeoxynucleotide inhibition as a potent diagnostic tool for gene function in plant biology

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Christer; Sun, Chuanxin; Ghebramedhin, Haile; Hoglund, Anna-Stina; Jansson, Christer

    2008-01-15

    -signaling proteins in pollen tubes from the lilly Agapanthus umbellatus. For the uptake of DNA pollen tubes represent a unique system since the growing tip is surrounded by a loose matrix of hemicellulose and pectins, exposing the plasma membrane7 and the first uptake of ODNs by pollen tubes was reported as early as 1994. A breakthrough in the employment of antisense ODN inhibition as a powerful approach in plant biology was recently presented through our work on intact barley leaves. As was illustrated by confocal microscopy and fluorescently labeled ODNs, naked ODNs were taken up through the leaf petiole and efficiently imported into the plant cell and the nucleus. The work portrayed in that study demonstrate the applicability of antisense ODN inhibition in plant biology, e.g. as a rapid antecedent to time-consuming transgenic studies, and that it operates through RNase H degradation. We employed the antisense ODN strategy to demonstrate the importance of the SUSIBA2 transcription factor in regulation of starch synthesis, and to depict a possible mechanism for sugar signaling in plants and how it might confer endosperm-specific gene expression during seed development. We also described the employment of the antisense ODN strategy for studies on in vitro spike cultures of barley. Here we present further evidence as to the value of the antisense ODN approach in plant biology by following the effects on starch branching enzyme (SBE) accumulation in barley leaves after suppression of individual SBE genes. In agreement with transcript analyses of SBE expression in barley leaves, a zymogram assay (Fig. 1) revealed that sucrose treatment of barley leaves increased the number of SBE activity bands as compared to sorbitol treatment. In the presence of antisense SBEI or SBEIIA ODNs, zymograms of sucrose-treated leaves displayed only a subset of these activities with bands in the top portion of the zymogram gel missing or diminished. With antisense SBEIIB ODN, all activity bands in the top

  3. Especially for High School Teachers

    Science.gov (United States)

    Emory Howell, J.

    1999-11-01

    many of our readers. The High School/College Interface Luncheon was part of the very rich day-long High School Program at the New Orleans ACS Meeting. Shown here (from left) are Glenn Crosby, the luncheon speaker; Lillie Tucker-Akin, the High School Day program chair; and Fred Johnson, Assistant Superintendent of Shelby County (TN) schools and Immediate Past President of NSTA. The recipient of the James Bryant Conant Award in High School Chemistry Teaching is Frank G. Cardulla, who taught for many years at Niles North High School, Skokie, Illinois. His extensive record of service to fellow teachers includes editing the JCE "View from My Classroom" feature for several years and writing several articles, as well as his recent appointment to the JCE Board of Publication. The recipient of the George C. Pimentel Award in Chemical Education is Jerry A. Bell of the American Chemical Society in Washington, DC. An author of numerous articles appearing in JCE and a member of the JCE Board of Publication for several years, he currently serves as Board Chair. The 16th Biennial Conference on Chemical Education Readers who attended the 15th BCCE in Waterloo, Ontario, know that much of the programming at these conferences is of interest to high school teachers. Many work shops, papers, and demonstrations are presented by high school teachers. There are many other outstanding papers and posters, plenary speakers, and exciting demonstrations. The 16th BCCE will be held at the University of Michigan in Ann Arbor, July 30-August 3, 2000. Among the high school teachers already scheduled to present workshops at the 16th BCCE are George Hague, Lynn Hershey, and Jack Randall, and there will be many more before the program is completed. The High School Chemistry Program Chair is Tim Graham, Roosevelt High School (MI). The Organizing Committee is seeking the assistance of local sections of the American Chemical Society within a 300-mile radius of Ann Arbor in providing support for high school

  4. Somatic growth effects of intramuscular injection of growth hormone in androgen-treated juvenile Nile tilapia, Oreochromis niloticus (Perciformes: Cichlidae

    Directory of Open Access Journals (Sweden)

    Marco A. Liñán-Cabello

    2013-03-01

    por tanque, en un período de seis semanas. Los tratamientos fueron: a peces tratados con 17-MT+HC en aceite mineral (RGH, b peces tratados con 17-MT+aceite mineral sin la adición de HC (R, c los peces que no fueron tratados con 17-MT-tratado+HC en aceite mineral (NGH, y d los peces que no fueron tratados con 17-MT+aceite mineral (N. La hormona de crecimiento humano recombinante (Humatrope, Eli Lilly & Co., Windlesham, Inglaterra, se inyectó en el pez con una dosis de 0.625mg por gramo de peso corporal. Los datos morfométricos se registraron al comienzo del experimento (T y en los días 15, 30 y 45 (T, T y T, Se registraron diversos indicadores de crecimiento: factor de condición (K, porcentaje de supervivencia (S, la tasa de conversión alimenticia (FCR, porcentaje de ganancia de peso (GP y el aumento de peso al día. El nivel óptimo dietético fue calculado suponiendo 5% de conversión de alimentos al peso total de cada grupo. Durante el experimento fue usada una dieta comercial con el 45% de proteína. De los resultados presentados, es evidente que la inyección de HC dio lugar a una mayor ganancia de peso en el 17-MT-los peces tratados (el grupo de tratamiento RGH, y la diferencia fue significativa, tanto en T y T (p<0.05 para ambas comparaciones. De manera similar, los altos valores de K se presentaron en los tratamientos R y RGH durante los primeros días de cultivo. Esto puede haber sido asociado con un mejor estado nutricional que afectó tanto el desarrollo de peso y la longitud del cuerpo del pez, como resultado del efecto aditivo de 17-MT y GH. Los tratamientos no andrógenos y los grupos tratados con andrógenos y con HC mostraron un mayor incremento en la ganancia de peso por día, los mayores valores de K y menores tasas de conversión del alimento, lo que sugiere una mayor eficiencia de la alimentación en los peces tratados con hormonas. Peces en el tratamiento RGH mostraron el mayor crecimiento, lo que sugiere una posible interacción entre el 17

  5. 国产与进口重组人胰岛素注射液Beagle犬皮下注射的生物等效性研究%Bioequivalence of domestic and imported recombinant human insulin injections after sc administration in Beagle dogs

    Institute of Scientific and Technical Information of China (English)

    申文晋; 宋紫辉; 范明源; 项宗尚; 蔡永明; 张宗鹏

    2014-01-01

    目的:以美国礼来公司重组人胰岛素注射液(优泌林R,Humulin R)为对照品,评价国产重组人胰岛素注射液(Insulin R)的相对生物利用度和生物等效性。方法采用自身随机交叉给药方案,12只健康Beagle犬分别sc同剂量Insulin R和Humulin R,按设计采集6 h内动态血标本。采用罗氏血糖仪与检测血药浓度同步测定动物血糖水平;放射免疫分析(RIA)法检测血药浓度;试验数据采用DAS 3.0药动学程序拟合计算参数,并进行生物等效性分析。结果 Beagle犬自身交叉sc Insulin R和Humulin R 0.5 U/kg后的血浆最低葡萄糖浓度(Cmin)分别为(1.6±0.4)、(1.6±0.2)mmol/L;达到最低浓度所需时间(tmin)分别为(1.0±0.5)、(1.1±0.6)h。Insulin R和Humulin R的主要药动学参数均值分别为:达峰时间(tmax)为(0.43±0.21)、(0.42±0.09)h;峰浓度(Cmax)为(203.2±63.3)、(193.5±63.1)μU/mL;药时曲线下面积(AUC0-6 h)为(281.2±47.5)、(266.6±62.5)μU/(mL·h);受试药Insulin R相对于对照药Humulin R的相对生物利用度为(109.4±25.5)%。结论两种重组人胰岛素注射剂在健康Beagle犬体内具有生物等效性。%Objective To assess the pharmacokinetic and bioequivalence of two formulations of recombinant human insulin injection, using locally manufactured Insulin R as test and Humulin R (Eli Lilly and Company) as reference. Methods Twelve Beagle dogs were assigned into two groups in which the dogs were sc given Insulin R and Humulin R at the dose of 0.5 U/kg according to a randomized two-phase crossover. The plasma concentration of Insulin R and Humulin R at 6 h intervals was determined using radioimmunoassay (RIA) method with the time course of changes in blood glucose level monitored. The pharmacokinetic parameters were calculated by DAS 3.0 software. Results Beagle dogs were treated with Insulin R and Humulin R following single

  6. Especially for High School Teachers

    Science.gov (United States)

    Howell, J. Emory

    1999-08-01

    Care to Share? An Informal Syllabus Exchange A recent email message from Thomas Shiland, who teaches at Saratoga Springs Senior High School, noted that the process of revising the high school chemistry syllabus is underway in New York State. He expressed a strong interest in helping construct a chemistry syllabus that represents the best thinking about appropriate content. He wondered if it would be possible to develop a way in which different secondary chemistry syllabi could easily be exchanged. It is likely that readers from other states and countries are involved in a similar process and might also be interested in exchanging syllabi. Many states do not use the term syllabus to describe their guiding curricular document for chemistry but rather refer to it as a framework or as guidelines. In most cases, the document includes a list of key ideas or topics, performance indicators, and the major understandings associated with each key idea. Such documents would be appropriate for exchange among those of you involved in the revision process. If you are interested in arranging an exchange please contact me by email at j.e.howell@usm.edu or by mail at J. E. Howell, Box 5043, USM, Hattiesburg, MS39406-5043, USA. High School Day Information The High School Chemistry Program at the American Chemical Society National Meeting in New Orleans, Louisiana will be held Sunday, August 22, 1999, at the Doubletree Hotel, 300 Canal Street. If you wish to register only for the High School Day activities, which includes a pass to the ACS Exposition, a special registration form is available from Lillie Tucker-Akin, 2800 Reynard Dr., Tupelo, MS38801; sci4me@aol.com; fax: 662/566-7906. Advance registration is 25 and the cost of the High School Luncheon is 12. Register in advance by August 1, 1999, or from 7:45 to 8:30 a.m. at the High School Day table in the conference room area of the Doubletree. The workshop schedule is shown below. Secondary School Feature Articles * Exploring the

  7. AMCP Partnership Forum: Enabling the Exchange of Clinical and Economic Information Pre-FDA Approval.

    Science.gov (United States)

    2017-01-01

    , since PIE is a novel category of information. New legislation could provide a safe harbor and clarity that PIE does not violate preapproval promotion and the Federal Food, Drug, and Cosmetic Act and its regulations. The AMCP Partnership Forum on Enabling the Exchange of Clinical and Economic Data Pre-FDA Approval and the development of this proceedings document were supported by AbbVie, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb, Celgene, Intarcia Therapeutics, Eli Lilly and Company, GlaxoSmithKline, Merck, National Pharmaceutical Council, Novo Nordisk, Pfizer, Pharmaceutical Research and Manufacturers of America, Precision for Value, Sanofi, Takeda Pharmaceuticals, U.S.A., and Xcenda. All sponsors participated in the forum and in revising and approving the manuscript.

  8. Book Reviews

    Directory of Open Access Journals (Sweden)

    R. de Ridder

    1986-01-01

    + 182 pp. - Anke Niehof, Imke Swart, Die Traditionellen Grundlagen der Erziehung im Zentralen Java, Wiesbaden: Franz Steiner Verlag, 1983. (130 pp. - J.H.B. den Ouden, R.S. Khare, The untouchable as himself. Ideology, identity and pragmatism among the Lucknow Chamars, Cambridge studies in cultural systems, Cambridge University Press, 1984. - Rien Ploeg, James A. Boon, Other tribes, other scribes; symbolic anthropology in the comparitive study of cultures, histories, religions, and texts, Cambridge: Cambridge University Press, 1982. xiv + 303 pp., appendixes. - Frank N. Pieke, Rubie S. Watson, Inequality among brothers: Class and kinship in South China, Cambridge: Cambridge University Press, 1985. xiii + 193 pp., 3 maps. - Rien Ploeg, Durk Hak, Watching the seaside. Essays on maritime anthropology. A. H. J. Prins; Festschrift on the occasion of his retirement from the Chair of Anthropology, University of Groningen, University of Groningen, 1984, 251 pp., ill., diagr., Ybeltje Kroes, Hans Schneymann (eds. - Rien Ploeg, Ladislav Holy, Actions, norms and representations. Foundations of anthropological inquiry. Cambridge: Cambridge University Press, 1983. VIII + 134 pp., Milan Stuchlik (eds. - Rien Ploeg, Nancy L. Hamblin, Animal use by the Cozumel Maya, Tucson, Arizona: The University of Arizona Press, 1984. 206 pp. - Ronald H. Poelmeijer, Lilly Eversdijk Smulders, Een jaar bij de yogiýs van India en Tibet, Deventer 1983. - Ype H. Poortinga, Dean Peabody, National characteristics, Cambridge/Paris: Camnbridge University Press/Editions de la Maison des Sciences de lýHomme, 1985. - Karen Portier, Khin Thitsa, Nuns, mediums and prostitutes in Chiengmai: A study of some marginal categories of women (41 pp.. - Karen Portier, Signe Howell, Chewong women in transition: The effects of monetization on a hunter-gatherer society in Malaysia (34 pp.. - Karen Portier, Maila Stivens, Sexual politics in Rembau: Female autonomy, matriliny and agrarian change in Negeri Sembilan, Malaysia

  9. A Personalised, Sensor-Based Smart Phone Intervention for Physical Activity and Diet – PRECIOUS N-of-1 Trial

    Directory of Open Access Journals (Sweden)

    Johanna Nurmi

    2015-10-01

    , including reminders, prompts, customised support, measurement, and gamified feedback and reward mechanisms. The novelty of PRECIOUS is based on two factors: (1 a virtual individual model, synthesised from self-reported and sensor parameters, which tailors suggestions to the user, and (2 a motivational service design framework combined with gamification principles to trigger, monitor, and sustain behaviour change, especially designed for individuals with low motivation or intention to act. Aims: This study will establish the feasibility of the PRECIOUS app and examine the effects of various components of PRECIOUS on physical activity with an N-of-1 study design (Lillie et al., 2011. More specifically, the study will identify which service features/behaviour change techniques (BCTs were most used and appreciated by individual users (Michie et al., 2013; investigate whether the use of motivational components leads to greater use of action components, and whether increased use of motivational and action components lead to increases in physical activity. Method/Results: Twelve inactive adults will be recruited to a six-week N-of-1 study testing a new smart phone application and activity bracelet. At baseline and post-treatment, participants will complete questionnaires assessing constructs related to self-determination theory and the health action process approach for both physical activity and healthy eating behaviours, and a 3-day heart rate variability measurement (FirstBeat Ltd; Helsinki, Finland to assess activity level and stress response. Objective physical activity and sleep data will be collected throughout the study using aggregated data gathered from the smartphone’s on-board accelerometer and an activity bracelet. After completion of the study, interviews with participants will qualitatively examine feasibility and acceptability of the interventions and examine possible reasons why the intervention techniques were or were not effective for each participant. The

  10. 奥氮平与氟哌啶醇治疗老年性谵妄的随机对照观察%Olanzapine and haloperidol for senile delirium: A randomized controlled observation

    Institute of Scientific and Technical Information of China (English)

    胡华; 邓伟; 杨辉; 刘玉

    2006-01-01

    啶醇组次之,对照组起效最慢(P<0.01).结论:奥氮平与氟哌啶醇治疗老年性谵妄疗效相当,但奥氮平起效更快.%BACKGROUND: Delirium is an acute organic brain syndrome caused by various reasons, and it is common in elderly patients. Antipsychotics treatment is an important method to control delirium.OBJECTIVE: To observe the efficacy of new antipsychotic agent of olanzapine and the traditional antipsychotic agent of haloperidol in treating senile delirium.DESIGN: A randomized controlled observation. SETTING: Mental Health Center, the First Affiliated Hospital of Chongqing University of Medical Sciences.PARTICIPANTS: Totally 175 inpatients with senile delirium were selected from the First Affiliated Hospital of Chongqing University of Medical Sciences from September 2001 to September 2003, they were randomly divided into olanzapine treatment group (n=74), haloperidol treatment group (n=72) and a control group(n=29). There were 111 males (63.4%) and 64 females (36.6%). Delirium had occurred for a duration of 30 minutes to 17 days, with an average of (3.02±2.71) days. The enrolled patients were classified according to the etiological factors of delirium: metabolic (n=68), toxic (n=47), structural (n=25) and infectious (n=35).METHODS: Different treatments were used in different groups. Control group (n=29): The patients were only given somatic treatment aiming at delirium, and not any drug for central nervous system was used. Olanzapine group (n=74): Besides the somatic treatment aiming at delirium, the patients were given olanzapine (Zyprexa, produced by Eli Lilly and Company,5 mg/tablet) taken orally or sublingually (fasted patients), the initial dosage was 1.25-2.5 mg per day, and then adjusted to 1.25-20 mg per day. Haloperidol group (n=72): Besides the somatic treatment aiming at delirium, they were treated with intramuscular injection of haloperidol (2.5-10 mg per day). The effects were prospectively observed for 1 week.The scores were observed before enrollment

  11. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2011-02-01

    The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

  12. 009 用牙本质粘结体系将复合物粘结到贱金属合金上的强度

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    轻吹干,直到底胶上出现有光泽的外观。将Optibond FL粘合剂应用到涂过底胶的金属上,光聚合30s。八组试样用All-Bond2材料处理,将等量的底胶A和B混合5s,在金属表面连续涂5层A和B混合底胶,用轻气流吹干底胶15s。然后应用牙本质/牙釉质结合树脂,用干的压缩空气吹薄,光聚合20s。将Herculite杂后复合物装入5号凝胶囊(Eli Lilly)中直到胶囊略微超填,然后将充填复合物胶囊的开口端放在预备好的金属表面上,用牙科探针从胶囊/金属界面除去多余的复合物溢出部分(flash),然后用超过400勒克司(lux)的光强度从3个角度光聚合复合物,每个角度30s,因此,总共3个30s暴光用于聚合复合物,2hr后除去凝胶囊。用MTS System 810机械测试体系从金属上折裂复合物,记录力的大小,进行统计学分析。1~8组的剪切结合强度值(MPa)分别为:12.04±2.26、12.26±3.28、12.20±2.50、14.26±2.83、11.91±2.04、12.96±2.87、14.42±2.75、16.72±3.50。一步方差分析揭示,8个粘结体系之间有显著性差异(p=0.002),多项t检验揭示All-Bond2组值最高,显著高于除3M Single Bond和Optibond FL组以外的其它5组。第5组值最低,显著低于All-Bond 2和Optibond FL组。单组份体系组和多组份体系组剪切结合强度没有显著性差异。牙本质粘合剂体系比树脂粘固剂体系显示出更高的剪切结合强度。应用底胶没有提高Pananvia 21的剪切结合强度。 (刘 玲摘 汪大林校)

  13. Obituary: Gary Lars Grasdalen, 1945-2003

    Science.gov (United States)

    Strom, Stephen Eric

    2003-12-01

    With the passing of Gary Grasdalen on 20 April 2003 the astronomical community has lost one its most creative members. Born in Albert Lea, Minnesota on 7 October 1945 to the farming family of Lars G. and Lillie Grasdalen, Gary developed a strong childhood interest in science, and a particular fascination with astronomy. In 1964, he entered Harvard College intending to pursue those interests. During his freshman year, Gary enrolled in an undergraduate research seminar in which he first displayed the combination of keen insight and imagination in applying new techniques that was manifest throughout his professional career. In 1968, he published his first two papers---studies of the C12/C13 ratio in metal deficient stars, and of Fe I and Fe II transition probabilities---which summarized research carried out during his junior and senior years at Harvard. Grasdalen next entered the astronomy graduate program at the University of California, Berkeley. There he developed a strong interest in the early stages of stellar evolution and, in particular, the potential of S-1 image intensifiers and newly available near-infrared detectors to detect and analyze the stellar populations embedded within their parent molecular cloud complexes. Following award of his PhD in 1972, Grasdalen was appointed to the staff at the Kitt Peak National Observatory. Early in his career at KPNO, Gary developed tools that enabled routine near-infrared mapping of nearby molecular cloud complexes, most notably the telescope control programs that enabled precise raster scanning of these regions. Those same programs were some of the many innovations in which Gary had a hand. These innovations enabled a generation of KPNO observers in the 1970s to fully exploit the power of the newly commissioned Mayall telescope as well as the smaller telescopes on Kitt Peak. In 1973, he published the first map of the central region of a molecular cloud, which revealed an extensive embedded, optically obscured

  14. Guidelines, Editors, Pharma And The Biological Paradigm Shift

    Directory of Open Access Journals (Sweden)

    Ajai R. Singh

    2007-01-01

    Full Text Available Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both. There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin and the marketing maneuvers of Eli Lilly's Xigris (rhAPC. Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour. A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.Clinical practice guidelines (CPG are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For

  15. Guidelines, editors, pharma and the biological paradigm shift.

    Science.gov (United States)

    Singh, Ajai R; Singh, Shakuntala A

    2007-01-01

    Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a

  16. Monograph: Concluding Remarks

    Directory of Open Access Journals (Sweden)

    Ajai R. Singh

    2007-01-01

    Full Text Available Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. There are significant costs involved too. Major areas of conflict of interest especially applicable to biomedical research have arisen, as academia interacts with industry. Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin and the marketing maneuvers of Eli Lilly's Xigris (rhAPC. A voluntary moratorium over pharma spending to pamper drug prescribers is necessary.The integrity of industry-sponsored clinical research has come under increasing scrutiny. The basic shizm is between the value system of a patient welfare driven professional and that of a profit driven industry . While one wants to avoid control but wants the dough, the other wants to exercise the control by supplying the dough. Clinical practice guidelines (CPG are considered important as they guide diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, dosages and criteria for selection. Besides clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a recent survey it was found that about 60% of 192 authors of clinical practice guidelines reported they had financial connections with the companies whose drugs were under consideration. This finding casts serious doubt on the credibility of this important pillar of modern clinical practice. It needs urgent reparative action. One of them is prospective and retrospective disclosure of financial conflict of interest by authors of CPGs.A Conference on Guideline Standardization (COGS was convened in April 2002 'to define a standard for guideline reporting that would promote guideline quality and facilitate implementation'. It includes items for

  17. News & Announcements

    Science.gov (United States)

    1999-09-01

    for travel awards for post-doctoral, graduate, and undergraduate women to make their first research presentation at a national meeting sponsored by Eli Lilly & Co. For more information and an application form, contact your department chair; http://www.tamug.tamu.edu/ascwcc; or Cheryl Brown, ACS, 1155 16th Street, NW, Washington, DC 20036; phone: 800/227-5558 ext. 6022; email c_brown@acs.org. The deadline for receipt of applications for meetings between January 1 and June 30, 2000, is October 15, 1999; for meetings between July 1 and December 31, 2000, the deadline is March 15, 2000. Call for Symposia, Papers, Workshops: 16th BCCE The 16th Biennial Conference on Chemical Education will be held July 30­August 3, 2000, at the University of Michigan in Ann Arbor. The conference Web site at http://www.umich.edu/ bcce is ready to accept proposals for symposia, papers, posters, and workshops. Or proposals may be submitted in writing to the Program Chair, Brian Coppola, phone: 734/764-7329; email: bcoppola@umich.edu. The deadline for submission of proposals for symposia and workshops is December 13, 1999; the deadline for submission of abstracts of papers and posters is February 4, 2000. For general information contact Seyhan Ege, phone: 734/764-7340; email: snege@umich.edu. 16th IUPAC Conference on Chemical Thermodynamics 16th IUPAC Conference on Chemical Thermodynamics (concurrent with 55th Calorimetry Conference and 10th Symposium on Thermodynamics of Nuclear Materials) August 6­11, 2000 Halifax, Nova Scotia, Canada This conference will cover research topics in all areas of thermodynamics. In addition, there will be a special poster session for papers on two aspects of thermodynamics education: lecture demonstrations and undergraduate laboratory experiments. Come and join us for lobster and learn what is new and exciting in thermodynamics. To be on the email list for this meeting, send a message to: ICCT@IS.DAL.CA. For further details, consult the conference Web site